Institute of Biochemistry, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Köln, Germany
Accepted on December 1, 1999;
Key words: mucin/MUC1/O-glycosylation/tumor antigen/cancer
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Introduction |
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Two important observations, which were made during the 1980s, have changed this view and conferred the mucins increased attraction as a research topic. Using advanced methodology and sophisticated instrumentation (FABMS, 500 MHz H-NMR) several groups could demonstrate by means of structural chemistry that mucins are much more complex glycosylated than expected (Lamblin et al., 1984; Hanisch et al., 1985
, 1986; Hounsell et al., 1985
, 1989; Mutsaers et al., 1986
). A second major point was the identification of tumor-associated epitopes on mucins as immunotargets on malignant epithelial cells and their secretions (Magnani et al., 1983
; Hilkens et al., 1984
; Burchell et al., 1987
). In particular the latter aspect has driven tremendous efforts to characterize distinct mucin species by recombinant technology. In 1990 four groups were able to sequence the first human mucin gene on the DNA level (Gendler et al., 1990
; Lan et al., 1990
; Ligtenberg et al., 1990
; Wreschner et al., 1990
). Designated as MUC1 in accord with the Human Genome Mapping conventions, this mucin protein is identical to the polymorphic epithelial mucin (PEM), the polymorphic urinary mucin (PUM), Episialin, DF3 antigen, and several other glycoforms of MUC1 isolated from various sources. MUC1 and meanwhile a series of other human mucins (MUC2 to MUC12) have revealed to exhibit large domains of tandemly repeated peptides as a structural characteristic of the "real" mucins (Porchet et al., 1991
; Bobek et al., 1993
; Toribara et al., 1993
; Gum et al., 1994
; Meerzaman et al., 1994
; Shankar et al., 1994
; Van Klinken et al., 1997
; Lapensee et al., 1997
; Nollet et al., 1998
; Williams et al., 1999
). They can be discriminated in this way from mucin-like glycoproteins, like GlyCAM1 or MadCAM1, serving roles in cell adhesion (Shimizu and Shaw, 1993
). The currently known MUC species can be subdivided into two groups dependent on their structural aspects and biosynthetic routes. Membrane bound mucins (MUC1, MUC3, MUC4, MUC12) exhibit hydrophobic sequences or "transmembrane domains" responsible for their anchoring in the lipid bilayer and C-terminal peptides enter the cytosol (Table I). With one exception (MUC7) the secretory mucins (MUC2, MUC5AC, MUC5B, MUC6) possess one or several von Willebrandt factor-like D domains (Table I), cystein-rich peptides, which function in the oligomerization of mucin monomers and in the packaging into secretory vesicles (Perez-Vilar and Hill, 1999
).
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MUC1 expression and function |
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Nonepithelial expression of the mucin has been described to occur on lymphoid cells and lymphomas, especially on plasma cells and myelomas (Zotter et al., 1988, and references therein; Treon et al., 1999
). The same authors described detection of the mucin also on anaplastic large cell lymphomas, some T lymphomas of the Ki-1 (activated) type, and on Reed-Sternberg cells in Hodgkin disease. Recently it was shown that a selected panel of anti-MUC1 antibodies stained positive with a fraction of normal proerythroblasts and erythroblasts in bone marrow (Brugger et al., 1999
). An important observation is furthermore that activated T cells, but not resting T lymphocytes switch on MUC1 expression (Agrawal et al., 1998
).
The cellular localization of MUC1 in normal ductal epithelia is restricted to the apical surface facing the lumen of the duct. There it may be responsible for the lubrication of the epithelial surfaces, and for the entrapment of particles or cellular debris. A potential protective function mediated by specific binding of ingested bacterial or viral pathogens was demonstrated for MUC1 in human milk (Schroten et al., 1992; Yolken et al., 1992
). While protective functions may be common to all mucins including the secreted species, the cytoplasmic tail of the membrane-integrated MUC1 has been proposed to be involved in cell signaling events (Pandey et al., 1995
). It contains potential tyrosine phosphorylation sites for binding to SH2 domains, like that on the adaptor protein Grb2. Although the functional role of MUC1 mediated cell signaling is unknown, there are hints that point to a possible involvement in cell adhesion (Yamamoto et al., 1997
). A cytoplasmic motif on MUC1 was identified to bind ß-catenin, and the interaction with this protein was demonstrated to be induced by adherence of epithelial cells to culture dishes. MUC1 interaction with ß-catenin is controlled by glycogen synthase kinase, which phosphorylates serine adjacent to proline in the STDRSPYE motif (Li et al., 1998
).
Among the numerous functions proposed for MUC1 its potential role in tumor progression and metastasis has to be emphasized. Malignant cells lose their polarity and MUC1 topology changes by expression also at the basolateral surface. Among other factors, this aberrant expression has been claimed to mediate the initial step in the metastatic cascade of tumor cells by the antiadhesive effects exerted by the rod-like, several hundred nanometer extending molecule that shields the cell surface sterically and electrostatically (Hilkens et al., 1992). In this way it is presumed to prevent the formation of cellcell contacts mediated by E-cadherin (Wesseling et al., 1996
) or cell matrix contacts mediated by integrins (Wesseling et al., 1995
). In the same way it may also be responsible for the escape of metastasizing tumor cells from the surveillance by the hosts immune system. This assumption is based on the finding that mucin-expressing cells are generally resistant to natural killer cells and cytotoxic T cells (Sherblom and Moody, 1986
). Moreover, MUC1 on tumor cells was demonstrated to induce a local T cell anergy (Agrawal et al., 1997
), an inhibition of proliferation which was reversible by interleukin-2. Finally, MUC1 has been identified in vitro as a potential target in the colonization of metastasizing tumor cells by interacting with ICAM1 (Regimbald et al., 1996
) or with E-selectin (Zhang et al., 1996
).
In line with these observations is the overexpression of mucin by carcinoma cells making MUC1 a primary target for tumor defense strategies. Since a fraction of the mucin is secreted or shed from the tumor cell surface, MUC1 is detectable in the sera of cancer patients and has meanwhile developed to an established tumor marker (Ca15.3) in the clinical postoperative diagnosis of breast cancer patients (Bon et al., 1990).
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Polymorphism of the MUC1 protein |
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The term polymorphism refers also to several isoforms of the mucin originating from alternative splicing events or from processing on the protein level (Figure 1). The membrane-associated MUC1 is expressed as a continuous polypeptide. However, between VNTR and transmembrane domains a proteolytic cleavage site is located which is used during processing of the mucin protein in the Golgi (Ligtenberg et al., 1992). Surface exposure of the cleavage products occurs by formation of a non-covalent heterodimeric complex composed of the mucin subunit and the C-terminal transmembrane unit which anchors MUC1 (Figure 1). This mode of membrane anchorage is not unique for MUC1, but has been reported also for the rat homologue of human MUC4, the ASGP-1/ASGP-2 complex (Sheng et al., 1990
). Two variant proteins that are generated by alternative splicing from the MUC1 gene form a similar complex (Baruch et al., 1999
). The MUC1/Y isoform, which is devoid of the tandem repeat domain (Zrihan-Licht et al., 1994
), spans the membrane and serves as a binding partner for another splice variant of the MUC1 gene, the secreted mucin-like polymorphic MUC1 protein MUC1/SEC (Figure 1), which contains a tandem repeat array (Baruch et al., 1999
). MUC1/SEC includes a C-terminal peptide sequence corresponding to parts of intron 2, but no transmembrane domain, and can be detected with sec-peptide specific antibodies in carcinoma cell secretions and in the sera of breast cancer patients.
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Polymorphism of MUC1 glycosylation |
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Tissue-specific glycosylation patterns
The structural features of O-linked glycans on MUC1 are common to mucin-type glycosylation, but vary in relation to organ- and differentiation-dependent fluctuations. MUC1 from lactating breast epithelium has been characterized to express primarily long polylactosamine-type chains (Hull et al., 1989; Hanisch et al., 1989
, 1990), which are built-up by elongation of the C6-branch of core2 (Figure 2A,B). This core-type, which is formed by branching of the Ser/Thr-linked GalNAc at C3 and C6, is the most frequent of the seven variants described so far on mucins (Table II). A minor fraction of the MUC1 glycans is derived from core 1-disaccharide (F.-G.Hanisch, A.M.Lawson, and T.Feizi, unpublished results), while the occurrence of the less frequent cores 3 and 4 or of the rarely expressed cores 5 to 7 (Table II) could not be demonstrated. The secretory glycoform in human milk is dominated by neutral glycans with linear and branched backbones, which can comprise up to 16 monosaccharide units. The repetitive N-acetyllactosamine units of the linear backbones were found to be linked via C3 or C6 of galactose (Hanisch et al., 1989
). Fucose is added to subterminal and internal GlcNAc residues in
4 and
3 linkages resulting in the formation of peripheral and repetitive Lewis type sequences (Figure 2B).
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Tumor-associated alterations of MUC1 O-glycosylation
In breast cancer the chain lengths of the O-linked glycans on MUC1 are restricted to the core-type level (Hanisch et al., 1996; Lloyd et al., 1996
), and sialylated glycans predominate over neutral ones (Figure 3). Enzymatic studies revealed that some mammary carcinoma cell lines and individual breast tumors do not express functional ß-glucosaminyltransferases (Brockhausen et al., 1995
), which is in accord with the glycan structures found on tumor-associated MUC1 (Figure 3). The low expression or even lack of the core2 forming ß6-glucosaminyltransferase in breast cancer cells (Brockhausen et al., 1995
) leads to an accumulation of core1-disaccharide, which serves as a substrate of Gal-specific
3-sialyltransferase and of GalNAc-specific ß6-sialyltransferases (Figure 3). There is evidence for overexpression of CMP-NeuAc : Galß13GalNAc
3-sialyltransferase in these cells, which may compete with the core 2 enzyme for substrate (Whitehouse et al., 1997
). In accord with this, the most prominent glycans found on MUC1 from T47D breast cancer cells were the trisaccharides NeuAc
23Galß13GalNAc and NeuAc
26(Galß13)GalNAc, and no Lewis antigens were detectable (Hanisch et al., 1996
). It has to be emphasized, however, that the outlined features of cancer-associated MUC1 are not shared by all breast cancer cell lines analyzed so far on the chemical level. An exceptionally high degree of complex glycosylation has been found on recombinant MUC1 glycosylation probes expressed in MCF-7 cells, which are able to synthetize GlcNAc-containing oligosaccharides with fucosylated Lewis-type epitopes (Lloyd et al., 1996
; S.Müller and F.-G.Hanisch, unpublished observations). On the other hand, T47D cell line can serve as a representative model, reflecting the alterations of O-glycosylation patterns in primary breast tumors in an extreme state. Another alteration of O-glycosylation, which is restricted to cancer-associated MUC1 and, hence, exhibits the qualities of a specific tumor marker in breast cancer, is the expression of the Hanganutsiu Deicher (HD) antigen. HD antigen is identical to an N-glycolyl sialic acid variant (NeuGc) that is not found in birds and man. However, gangliosides of oncofetal origin (Kawai et al., 1991
) and MUC1 from breast carcinoma cells (cell lines and solid tumors) were demonstrated immunochemically (Devine et al., 1991
) and chemically to contain this variant in a fraction of their sialic acids (Hanisch et al., 1996
).
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No structural or enzymatic evidence is currently available for tumor-associated MUC1 from other organ sites.
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Site-specific O-glycosylation of MUC1 |
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In the MUC1 model the site-specific GalNAc transfer to the five potential positions within the repeat peptide has been extensively studied in vitro (Nishimori et al., 1994; Stadie et al., 1995
). rGalNAc-T1 prefers the Thr within VTSA (Figure 4), but is able to glycosylate also the Ser and Thr residues in the GSTA motif (Wandall et al., 1997
; Hanisch et al., 1999
). On the other hand, rGalNAc-T2 transfers the sugar more rapidly to Thr within GSTA, while Thr in VTSA and Ser in GSTA are less efficient substrate positions. The remaining sites, Ser in VTSA and Thr in PDTR, cannot be glycosylated by these two enzymes, but it has been shown that the "fill-up" reactions are catalyzed by rGalNAc-T4 (Bennett et al., 1998
), an enzyme exhibiting a strict dependency on previous glycosylation. The concerted action of rGalNAc-T1, -T2, and -T4, and possibly also other rGalNAc-Ts, would expectedly yield a fully glycosylated MUC1 tandem repeat peptide (Figure 4). Whether a state of full glycosylation is reached or not may depend on several parameters: the cellular repertoire and activity of ppGalNAc-Ts and a postulated dynamic regulation of initial O-glycosylation considering epigenetic effects of previous glycosylation on the GalNAc transfer to other vicinal or proximal sites. Such glycosylation-induced effects have been demonstrated to exist in two in vitro studies (Brockhausen et al., 1996
; Hanisch et al., 1999
). While positive effects were revealed on the monosaccharide level of glycosylated MUC1 peptides, only negative influences were exerted by core 1-disaccharide on glycosylation at adjacent and distant sites. These antagonistic effects of mono- and di(oligo)saccharides could underlie a postulated regulatory mechanism, which assumes early competition of initial O-glycosylation with core glycan synthesis in the cis Golgi. A competition of ppGalNAc-Ts with the core-specific glycosyltransferases involved in core 1 and core 2 synthesis could finally determine the density of O-glycosylation (Figure 4).
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MUC1 O-glycosylation and immunogenicity/antigenicity |
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In the case of MUC1, the protein core, although heavily glycosylated, seems to elicit the stronger immune response in mice, since most hybridoma antibodies generated to this mucin bind to peptide epitopes within the VNTR domain (Price et al., 1997). The preferred target for most peptide-specific antibodies generated to the tumor mucin is located at the DTR motif within the repeat peptide (Price et al., 1997
). In humans, however, the natural B cell response to MUC1 shows a second immunogenic motif (Petrarca et al., 1996
). The most frequent minimal epitope of natural IgM and IgG in healthy subjects as well as in cancer patients was recently identified as RPAPGS, followed by PPAHGVT and PDTRP (von Mensdorff-Poilly et al., unpublished observations). Unlike the vaccine-induced antibodies the natural anti-MUC1 reacts more strongly to the glycosylated (GalNAc substituted) peptides. One would expect that glycosylation of the DTR motif, as in the case of a tumor-associated glycoform of the mucin, should reduce or abolish binding of antibodies directed to this peptide sequence. Recent evidence, however, suggests that glycosylation of the motif with core-type glycans increases its antigenicity rather than to reduce it (Karsten et al., 1998
). Among a series of DTR-specific hybridoma antibodies the majority showed this unexpected behavior (Table III). While recognition of the nonsubstituted DTR motif was demonstrated to be affected by proximal glycosylation (Stadie et al., 1995
), the fully glycosylated repeat peptide with GalNAc or Gal-GalNAc in each of the five positions exhibited similar binding activity as the singly, DTR-glycosylated TR peptide (Karsten et al., 1998
).
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MUC1 as T cell immunotarget
It remains to be established whether the glycosylation-induced effects on antigenicity of the DTR motif have impact also on its immunogenicity. B- and T-cell responses are dependent on the proteolytic processing and MHC presentation of the protein fragments, and currently only limited information is available on these processes with regard to normal mature or cancer-associated glycoforms of MUC1. Model studies with a nonimmunogenic peptide from hemoglobin that had been substituted with GalNAc and other short glycan moieties have indicated that core-type glycans on MHC class II presented peptides can be recognized by T cell receptors (Galli-Stampino et al., 1997; Jensen et al., 1997
). In accord with this, core 1 glycosylated TR peptides of MUC1 were able to induce strong, polyclonal proliferative responses of CD4+ T cells from both healthy donors and breast cancer patients (Burchell et al., Workshop on Carbohydrates and the Immune Response, Lesbos, 1999). The Th1 type response was independent of a presentation of the MUC1 glycopeptides by dendritic cells, but showed a strict dependency on the site of glycan substitution within the repeat peptide.
The first evidence that MUC1 can serve as a target antigen for tumor specific cytotoxic T cells (CTL) came from studies on breast cancer patients (Jerome et al., 1991). It could be demonstrated that tumor-reactive T cells from peritumoral lymph nodes of these patients were able to kill MUC1 positive cancer cells. The epitopes recognized by these T cells were localized within the VNTR domain of MUC1 and identified as the SM-3 defined PDTRP peptide motif (Jerome et al., 1991
). The mode of CTL activation was unusual, since it was independent of MUC1 processing and presentation. A likely explanation of these unexpected findings was the assumption that cross-linking of T cell receptors was mediated by their simultaneous binding to the repetitive epitopes within the VNTR domain of the mucin. Unfortunately, such a mode of CTL activation circumventing the participation of T helper cells results in responses of low efficacy. The induction of CD4+ T cell responses, however, seems to be critically dependent on the glycosylation state of MUC1. Secretory MUC1 glycoforms from tumor ascites exhibiting a high degree of complex O-glycosylation are unable to prime strong helper T cell responses when administered to dendritic cells in vitro (Hiltbold et al., 1998
). On the other hand, a synthetic peptide corresponding to five unglycosylated repeats primed CD4+ T cells from healthy donors when presented by dendritic cells (Hiltbold et al., 1998
). The naturally processed class II epitope was identified as the dodecapeptide PGSTAPPAHGVT, which was restricted to presentation by HLA-DR3. Other peptide epitopes of the VNTR domain had previously been shown to be restricted to HLA-A2 (Apostolopoulos et al., 1997
), and to HLA-A11 (Domenech et al., 1995
), but the responses were of low efficacy and T helper cell independent. In summary, the above findings clearly indicate that the healthy human peripheral T cell repertoire contains T helper cells capable of recognizing MUC1 epitopes on the nonglycosylated mucin peptide. Fully glycosylated MUC1 as found in tumor ascites is presumably not properly processed by the antigen presenting cells due to proteolytic resistance of the peptide core. This resistance is likely to be mediated by high density O-glycosylation of the tandem repeat peptides. Recent evidence suggests, on the other hand, that also glycosylated forms of MUC1 can be processed by dendritic cells. However, proteolytic cleavage and presentation are restricted to MHC class I and the efficiency of processing was shown to be inversely correlated with the degree of MUC1 peptide glycosylation (Hiltbold et al., 1999
).
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Concluding remarks and perspectives |
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Acknowledgments |
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Footnotes |
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References |
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Agrawal,B., Krantz,M.J., Parker,J. and Longenecker,B.M. (1998) Expression of MUC1 mucin on activated human T cells: implications for a role of MUC1 in normal immune regulation. Cancer Res., 58, 40794081.[Abstract]
Apostolopoulos,V. and McKenzie,I.F.C. (1994) Cellular mucins: targets for immunotherapy. Crit. Rev. Immunol. 14, 293309.[ISI][Medline]
Apostolopoulos,V., Karanikas,V., Haurum,J.S. and McKenzie,I.F. (1997) Induction of HLA-A2-restricted CTLs to the mucin 1 human breast cancer antigen. J. Immunol., 159, 52115218.[Abstract]
Baruch,A., Hartmann,M., Yoeli,M., Adereth,Y., Greenstein,S., Stadler,Y., Skornik,Y., Zaretzky,J., Smorodinsky,N.I., Keydar,I. and Wreschner,D.H. (1999) The breast cancer-associated MUC1 gene generates both receptor and its cognate binding protein. Cancer Res., 59, 15521561.
Bennett,E.P., Hassan,H., Mandel,U., Mirgorodskaya,E., Roepstorff,P., Burchell,J., Taylor-Papadimitriou,J., Hollingsworth,M.A., Merkx,G., Van Kessel,A.G., Eiberg,H., Steffensen,R., Clausen,H. (1998) Cloning of a human UDP-GalNAc: polypeptide N-acetylgalactosaminyl-transferase that complements other GalNAc-transferases in complete O-glycosylation of the MUC1 tandem repeat. J. Biol. Chem., 273, 3047230481.
Bennett,E.P., Hassan,H., Mandel,U., Hollingsworth,M.A., Akisawa,N., Ikematsu,Y., Merkx,G.,van Kessel,A.G., Olofsson,S. and Clausen,H. (1999) Cloning and characterization of a close homologue of human UDP-GalNAc: polypeptide N-acetylgalactosaminyl-transferase-T3, designated GalNAc-T6. Evidence for genetic but not functional redundancy. J. Biol. Chem., 274, 2536225370.
Bhavanandan,V.P., Zhu,Q., Yamakami,K., Dilulio,N.A., Nair,S., Capon,C., Lemoine,J. and Fournet,B. (1998) Purification and characterization of the MUC1 mucin-type glycoprotein, epitectin, from human urine: structures of the major oligosaccharide alditols. Glycoconj. J., 15, 3749.[ISI][Medline]
Bobek,L.A., Tsai,H., Biesbrock,A.R. and Levine,M.J. (1993) Molecular cloning, sequence and specificity of expression of the gene encoding the low molecular weight human salivary mucin (MUC7). J. Biol. Chem., 268, 2056320569.
Bon,G.G., Kenemans,P., van Kamp,G.J., Yedema,C.A. and Hilgers,J. (1990) Review on the clinical value of polymorphic epithelial mucin markers for the management of carcinoma patients. J. Nucl. Allied Sci., 34, 151162.
Brockhausen,I., Romero,P.A., Herscovics,A. (1991) Glycosyltransferase changes upon differentiation of CaCo-2 human colonic adenocarcinoma cells. Cancer Res. 51, 31363142.[Abstract]
Brockhausen,I., Yang,J.M., Burchell,J., Whitehouse,C. and Taylor-Papadimitriou,J. (1995) Mechanisms underlying aberrant glycosylation of MUC1 mucin in breast cancer cells. Eur. J. Biochem., 233, 607617.[Abstract]
Brockhausen,I., Toki,D., Brockhausen,J., Peters,S., Bielfeldt,T., Kleen,A., Paulsen,H., Meldal,M., Hagen,F. and Tabak,L.A. (1996) Specificity of O-glycosylation by colostrum UDP-GalNAc: polypeptide N-acetylgalactosaminyl-transferase using synthetic glycopeptide substrates. Glycoconj. J., 13, 849856.[ISI][Medline]
Brugger,W., Bühring,H.-J., Grünebach,F., Vogel,W., Kaul,S., Müller,R., Brümmendorf,T.H., Ziegler,B.L., Rappold,I., Brossart,P., Scheding,S. and Kanz,L. (1999) Expression of MUC1 epitopes on normal bone marrow: implications for the detection of micrometastatic tumor cells. J. Clin. Oncol., 17, 15351544.
Burchell,J., Taylor-Papadimitriou,J. (1993) Effect of modification of carbohydrate side chains on the reactivity of antibodies with core-protein epitopes of the MUC1 gene product. Epith. Cell Biol., 2, 155162.[ISI][Medline]
Burchell,J., Gendler,S., Taylor-Papadimitriou,J., Girling,A., Lewis,A., Millis,R. and Lamport,D. (1987) Development and characterization of breast cancer reactive monoclonal antibodies directed to the core protein of the human milk mucin. Cancer Res., 47, 54765482.
Clausen,H. and Bennett,E.P. (1996) A family of UDP-GalNAc: polypeptide N-acetyl- galactosaminyl-transferases control the initiaition of mucin-type O-linked glycosylation. Glycobiology, 6, 635646.[ISI][Medline]
Corfield,A.P., Myerscough,N., Gough,M., Brockhausen,I., Schauer,R. and Paraskeva,C. (1995) Glycosylation patterns of mucins in colonic disease. Biochem. Soc. Trans., 23, 840845.[ISI][Medline]
Devine,P.L., Clark,B.A., Birrel,G.W., Layton,G.T., Ward,B.G., Alewood,P.F. and McKenzie,I.F. (1991) The breast tumor-associated epitope defined by monoclonal antibody 3E1.2 is an O-linked mucin carbohydrate containing N-glycolylneuraminic acid. Cancer Res., 51, 58265836.[Abstract]
Dokurno,P., Bates,P.A., Band,H.A., Steward,L.M.D., Lally,J.M., Burchell,J.M., Taylor-Papadimitriou,J., Snary,D., Sternberg,M.J.E. and Freemont,P.S. (1998) Crystal structure at 1.95 A resolution of the breast tumor-specific antibody SM-3 complexed with its peptide epitope reveals novel hypervariable loop recognition. J. Mol. Biol., 284, 713728.[ISI][Medline]
Domenech,N., Henderson,R.A. and Finn,O.J. (1995) Identification of an HLA-A11-restricted epitope from the tandem repeat domain of the epithelial tumor antigen mucin. J. Immunol., 155, 47664774.[Abstract]
Finn,O.J., Jerome,K.R., Henderson,R.A., Pecher,G., Domenech,N., Magarian-Blander,J. and Barratt-Boyes,S.M. (1995) MUC1 epithelial tumor mucin-based immunity and cancer vaccines. Immunol. Rev., 145, 6189.[ISI][Medline]
Fontenot,J.D., Tjandra,N., Bu,D., Ho,C., Montelaro,R.C. and Finn,O.J. (1993) Biophysical characterization of one-, two- and three-tandem repeats of human mucin (MUC1) protein core. Cancer Res., 53, 53865394.[Abstract]
Fontenot,J.D., Mariappan,S.V., Catasti,P., Domenech,N., Finn,O.J. and Gupta,G. (1995) Structure of a tumor associated antigen containing a tandemly repeated immunodominant epitope. J. Biomol. Struct. Dyn., 13, 245260.[ISI][Medline]
Galli-Stampino,L., Meinjohanns,E., Frische,K., Meldal,M., Jensen,T., Werdelin,O. and Mouritsen,S. (1997) T-cell recognition of tumor-associated carbohydrates: the nature of the glycan moiety plays a decisive role in determining glycopeptide immunogenicity. Cancer Res., 57, 32143222.[Abstract]
Gendler,S.J. and Spicer,A.P. (1995) Epithelial mucin genes. Annu. Rev. Physiol., 57, 607634.[ISI][Medline]
Gendler,S.J., Taylor-Papadimitriou,J., Duhig,T., Rothbard,J. and Burchell,J. (1988) A highly immunogenic region of a human epithelial mucin expressed by carcinomas is made up of tandem repeats. J. Biol. Chem., 263, 1282012823.
Gendler,S.J., Lancaster,C.A., Taylor-Papadimitriou,J., Duhig,T., Peat,N., Burchell,J., Pemberton,L., Lalani,E. and Wilson,D. (1990) Molecuilar cloning and expression of the human tumor-associated polymorphic epithelial mucin PEM. J. Biol. Chem., 265, 1528615293.
Gooley,A.A. and Williams,K.L. (1994) Towards characterizing O-glycans: the relative merits of in vivo and in vitro approaches in seeking peptide motifs specifying O-glycosylation sites. Glycobiology, 4, 413417.[ISI][Medline]
Gum,J.R., Hicks,J.B., Toribara,N.W., Siddiki,B. and Kim,Y.S. (1994) Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the amino terminus and overall sequence similarity to prepro-von Willebrand factor. J. Biol. Chem., 269, 24402446.
Guyonnet Duperat,V., Audie, J-P., Debailleul,V., Laine,A., Buisine, M-P., Galiegue-Zouitina,S., Pigny,P., Degand,P., Aubert, J-P. and Porchet,N. (1995) Characterization of the human mucin gene MUC5AC: a consensus cysteine-rich domain for 11p15 mucin genes? Biochem. J. 305, 211219.[ISI][Medline]
Hagen,K.G., Hagen,F.K., Balys,M.M., Beres,T.M., Van Wuyckhuyse,B. and Tabak,L.A. (1998) Cloning and expression of a novel, tissue specifically expressed member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferase family. J. Biol. Chem., 273, 2774927754.
Hanisch,F.-G. (1998) Specificity clusters of MUC1-reactive mouse monoclonal antibodies. Tumor Biol., 19, 111117.[ISI]
Hanisch,F.-G., Egge,H., Peter-Katalinic,J. and Uhlenbruck,G. (1986) Primary structure of a major sialyl-saccharide alditol from human amniotic mucins expressing the tumor-associated sialyl-Lewis x antigenic determinant. FEBS Lett., 200, 4246.[ISI][Medline]
Hanisch,F.-G., Egge,H., Peter-Katalinic,J., Uhlenbruck,G., Dienst,C. and Fangmann,R. (1985) Primary structures and Lewis blood-group-dependent expression of major sialylated saccharides from mucus glycoproteins of human seminal plasma. Eur. J. Biochem., 152, 343351.[Abstract]
Hanisch,F.-G., Müller,S., Hassan,H., Clausen,H., Zachara,N., Gooley,A.A., Paulsen,H., Alving,K. and Peter-Katalinic,J. (1999) Dynamic epigenetic regulation of initial O-glycosylation by UDP-GalNAc:peptide N-acetyl- galactosaminyltransferases. J. Biol. Chem., 274, 99469954.
Hanisch,F.-G., Peter-Katalinic,J., Egge,H., Dabrowski,U. and Uhlenbruck,G. (1990) Structures of acidic O-linked polylactosaminoglycans on human skim milk mucins. Glycoconj. J., 7, 525543.[ISI][Medline]
Hanisch,F.-G., Stadie,T.R.E., Deutzmann,F. and Peter-Katalinic,J. (1996) MUC1 glycoforms in breast cancer: cell line T47D as a model for cancer-associated alterations of O-glycosylation. Eur. J. Biochem., 236, 318327.[Abstract]
Hanisch,F.-G., Uhlenbruck,G., Peter-Katalinic,J., Egge,H., Dabrowski,J. and Dabrowski,U. (1989) Structures of neutral O-linked polylactosaminoglycans on human skim milk mucins. J. Biol. Chem., 264, 872883.
Hilkens,J. and Buijs,F. (1988) Biosynthesis of MAM-6, an epithelial sialomucin. Evidence for involvement of a rare proteolytic cleavage step in the endoplasmic reticulum. J. Biol. Chem., 263, 42154222.
Hilkens,J., Buijs,F., Hilgers,J., Hageman,P., Calafat,J., Sonnenberg,A. and van der Valk,M. (1984) Monoclonal antibodies against human milk-fat globule membranes detecting differentiation antigens of the mammary gland and its tumors. Int. J. Cancer, 34, 197206.[ISI][Medline]
Hilkens,J., Ligtenberg,M.J-L., Vos,H.L. and Litvinov,S.V. (1992) Cell membrane associated mucins and their adhesion modulating property. Trends Biochem. Sci., 17, 359363.[ISI][Medline]
Hiltbold,E.M., Alter,M.D., Ciborowski,P. and Finn,O.J. (1999) Presentation of MUC1 tumor antigen by class I MHC and CTL function correlate with the glycosylation state of the protein taken up by dendritic cells. Cell. Immunol., 194, 143149.[ISI][Medline]
Hiltbold,E.M., Ciborowski,P. and Finn,O.J. (1998) Naturally processed class II epitope from the tumor antigen MUC1 primes human CD4+ T cells. Cancer Res., 58, 50665070.[Abstract]
Hounsell,E.F., Lawson,A.M., Feeney,J., Gooi,H.C., Pickering,N.J., Stoll,M.S., Lui,S.C. and Feizi,T. (1985) Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofetal antigens. Eur. J. Biochem., 148, 367377.[Abstract]
Hounsell,E.F., Lawson,A.M., Stoll,M.S., Kane,D.P., Cashmore,G.C., Carruthers,R.A., Feeney,J. and Feizi,T. (1989) Characterization by mass spectrometry and 500-MHz proton nuclear magnetic resonance spectroscopy of penta- and hexasaccharide chains of human fetal gastrointestinal mucins (meconium glycoproteins). Eur. J. Biochem., 186, 597610.[Abstract]
Hull,S.R., Bright,A., Carraway,K.L., Abe,M., Hayes,D.F. and Kufe,D.W. (1989) Oligosaccharide differences in the DF3 sialomucin antigen from normal human milk and the BT20 human breast carcinoma cell line. Cancer Commun., 1, 261267.[Medline]
Jensen,T., Hansen,P., Galli-Stampino,L., Mouritsen,S., Frische,K., Meinjohanns,E., Meldal,M. and Werdelin,O. (1997) Carbohydrate and peptide specificity of MHC class II-restricted hybridomas raised against an O-glycosylated self peptide. J. Immunol., 158, 37693778.[Abstract]
Jerome,K.R., Barud,D.L., Bendt,K.M., Boyer,C.M., Taylor-Papdimitriou,J., McKenzie,I.F.C., Bast,R.C. and Finn,O.J. (1991) Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by malignant cells. Cancer Res., 51, 29082916.[Abstract]
Karsten,U., Diotel,C., Klich,G., Paulsen,H., Goletz,S., Müller,S. and Hanisch,F.-G. (1998) Enhanced binding of antibodies to the DTR motif of MUC1 tandem repeat peptide is mediated by site-specific glycosylation. Cancer Res., 58, 25412549.[Abstract]
Kawai,T., Kato,A., Higashi,H., Kato,S. and Naiki,M. (1991) Quantitative determination of N-glycolylneuraminic acid expression in human cancerous tissues and avian lymphoma cell lines as a tumor-associated sialic acid by gas chromatography-mass spectrometry. Cancer Res., 51, 12421246.[Abstract]
Kirnarsky,L., Nomoto,M., Ikematsu,Y., Hassan,H., Bennett,E.P., Cerny,R.L., Clausen,H., Hollingsworth,M.A. and Sherman,S. (1998) Structural analysis of peptide substrates for mucin-type O-glycosylation. Biochemistry, 37, 1281112817.[ISI][Medline]
Kurosaka,A., Nakajima,H., Funakoshi,I., Matsuyama,M., Nagayo,T. and Yamashina,I. (1983) Structures of the major oligosaccharides from human rectal adenocarcinoma glycoprotein. J. Biol. Chem., 258, 1159411598.
Lamblin,G., Boersma,A., Lhermitte,M., Roussel,P., Mutsaers,J.H., van Halbeek,H. and Vliegenthardt,J.F. (1984) Further characterization, by combined high-performance liquid chromatography/1H-NMR approach, of the heterogeneity displayed by the neutral carbohydrate chains of human bronchial mucins. Eur. J. Biochem., 143, 227236.[Abstract]
Lan,M.S., Batra,S.K., Qui,W.-N, Metzgar,R.S. and Hollingsworth,M.A. (1990) Cloning and sequencing of a human pancreatic tumor mucin cDNA. J. Biol. Chem., 265, 1529415299.
Lapensee,L., Paquette,Y. and Bleau,G. (1997) Allelic polymorphism and chromosomal localization of the human oviductin gene (MUC9). Fert. Ster., 68, 702708.
Li,Y., Bharti,A., Chen,D., Gong,J. and Kufe,D. (1998) Interaction of glycogen synthase kinase 3ß with the DF3/MUC1 carcinoma-associated antigen and ß-catenin. Mol. Cell Biol., 18, 72167224.
Ligtenberg,M.J., Kruijshaar,L., Buijs,F., van Meijer,M., Litvinov,S.V. and Hilkens,J. (1992) cell-associated episialin is a complex containing two proteins derived from a common precursor. J. Biol. Chem., 267, 61716177.
Ligtenberg,M.J.L., Vos,H.L., Gennissen,A.M.C. and Hilkens,J. (1990) Episialin, a carcinoma associated mucin, is generated by a polymorphic gene encoding splice variants with alternative amino termini. J. Biol. Chem., 265, 55735578.
Litvinov,S.V. and Hilkens,J. (1993) The epithelial sialomucin, episialin, is sialylated during recycling. J. Biol. Chem., 268, 2136421371.
Lloyd,K., Burchell,J., Kudryashov,V., Yin,B.W.T. and Taylor-Papadimitriou,J. (1996) Comparison of O-linked carbohydrate chains in MUC1 mucin from normal breast epithelial cell lines and breast carcinoma cell lines. Demonstration of simpler and fewer glycan chains in tumor cells. J. Biol. Chem., 271, 3332533334.
Magnani,J.L., Steplewski,Z., Koprowski,H. and Ginsburg,V. (1983) Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 199 in the sera of patients as a mucin. Cancer Res., 43, 54895492.
Meerzaman,D., Charles,P., Daskal,E., Polymeropoulos,M.H., Martin,B.M. and Rose,M.C. (1994) Cloning and analysis of cDNA encoding a major airway glycoprotein, human tracheobronchial mucin (MUC5). J. Biol. Chem., 269, 1293212939.
Müller,S., Goletz,S., Packer,N., Gooley,A., Lawson,A.M. and Hanisch,F.-G. (1997) Localization of O-glycosylation sites on glycopeptide fragments from lactation-associated MUC1. J. Biol. Chem., 272, 2478024793.
Müller,S., Alving,K., Peter-Katalinic,J., Zachara,N., Gooley,A.A. and Hanisch,F.-G. (1999) High density O-glycosylation on tandem repeat peptide from secretory MUC1 of T47D breast cancer cells. J. Biol. Chem., 274, 1816518172.
Mutsaers,J.H., van Halbeek,H., Vliegenthardt,J.F., Wu,A.M. and Kabat,E.A. (1986) Typing of core and backbone domains of mucin-type oligosaccharides from human ovarian-cyst glycoproteins by 500-MHz 1H-NMR spectroscopy. Eur. J. Biochem., 157, 139146.[Abstract]
Nishimori,I., Johnson,N.R., Sanderson,S.D., Perini,R., Mountjoy,K., Cernag,R.L., Gross,M.L. and Hollingsworth,M.A. (1994) Influence of acceptor substrate primary amino acid sequence on the activity of human UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase. J. Biol. Chem., 269, 1612316130.
Nollet,S., Moniaux,N., Maury,J., Petitprez,D., Degand,P., Laine,A., Porchet,N. and Aubert,J.P. (1998) Human mucin gene MUC4: organization of its 5'-region and polymorphism of its central tandem repeat array. Biochem. J., 332, 739748.[ISI][Medline]
Pandey,P., Kharbanda,S. and Kufe,D. (1995) Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein. Cancer Res., 55, 40004003.[Abstract]
Perez-Vilar,J. and Hill,R.L. (1999) The structure and assembly of secreted mucins. J. Biol. Chem., 274, 3175131754.
Petrarca,C., Rughetti,A., Rahimi,H., Dagostini,F., Turchi,V., Ghetti,C.A., Scambia,G., Frati,L. and Nuti,M. (1996) Human antibodies against the polymorphic epithelial mucin in ovarian cancer patients recognize a novel sequence in the tandem repeat region. Eur. J. Cancer, 32A, 21552163.
Podolski,D.K. (1985) Oligosaccharide structures of human colonic mucin. J. Biol. Chem., 260, 82628271.
Podolsky,D.K., (1985) Oligosaccharide structures of isolated human colonic mucin species. J. Biol. Chem., 260, 1551015515.
Porchet,N., Nguyen,V.C., Dufosse,J., Audie,J.P., Guyonnet-Duperat,V., Gross,M.S., Denis,C., Degand,P., Bernheim,A. and Aubert,J.P. (1991) Molecular cloning and chromosomal localization of a novel human tracheo-bronchial mucin cDNA containing tandemly repeated sequences of 48 base pairs. Biochem. Biophys. Res. Commun., 175, 414422.[ISI][Medline]
Price,M.R. and 59 coauthors (1997) Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1mucin. Tumor Biol., 19 (Suppl. 1), 120.
Regimbald,L.H., Pilarski,L.M., Longenecker,B.M., Reddish,M.A., Zimmermann,G. and Hugh,J.C. (1996) The breast mucin MUC1 as a novel adhesion ligand for endothelial intercellular adhesion molecule 1 in breast cancer. Cancer Res., 56, 42444249.[Abstract]
Scanlon,M.J., Morley,S.D., Jackson,D.E., Price,M.R. and Tendler,S.J. (1992) Structural and computational investigations of the conformation of antigenic peptide fragments of human polymorphic epithelial mucin. Biochem. J., 284, 137144.[ISI][Medline]
Schroten,H., Hanisch,F.-G., Plogmann,R., Hacker,J., Uhlenbruck,G., Nobis-Bosch,R. and Wahn,V. (1992) Inhibition of adhesion of S-fimbriated Escherichia coli to buccal epithelial cells by human milk fat globule membrane components: a novel aspect of the protective function of mucins in the nonimmunoglobulin fraction. Infect. Immun., 60, 28932899.[Abstract]
Shankar,V., Gilmore,M.S., Elkins,R.C. and Sachdev,G.P. (1994) A novel human airway mucin cDNA encodes a protein with unique tandem-repeat organization. Biochem. J., 300, 295298.[ISI][Medline]
Sheng,Z.Q., Hull,S.R. and Carraway,K.L. (1990) Biosynthesis of the cell surface sialomucin complex of ascites 13762 rat mammary adenocarcinoma cells from a high molecular weight precursor. J. Biol. Chem., 265, 85058510.
Sherblom,A.P. and Moody,C.E. (1986) Cell surface sialomucin and resistance to natural cell-mediated cytotoxicity of rat mammary tumor ascites cells. Cancer Res., 46, 45434546.[Abstract]
Shimizu,Y. and Shaw,S. (1993) Cell adhesion. Mucins in the main stream. Nature, 366, 630631.[ISI][Medline]
Siddiqui,J., Abe,M., Hayes,D., Shani,E., Yunis,E., Kufe,D. (1988) Isolation and sequencing of a cDNA coding for the human DF3 breast carcinoma-associated antigen. Proc. Natl. Acad. Sci. USA, 85, 23202323.[Abstract]
Spicer,A.P., Parry,G., Patton,S. and Gendler,S.J. (1991) Molecular cloning and analysis of the mouse homologue of the tumor-associated mucin, MUC1, reveals conservation of potential O-glycosylation sites, transmembrane and cytoplasmic domains and a loss of minisatellite-like polymorphism. J. Biol. Chem., 266, 1509915109.
Stadie,T., Chai,W., Lawson,A.M., Byfield,P. and Hanisch,F.-G. (1995) Studies on the order and site-specificity of GalNAc-transfer to MUC1 tandem repeats by UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase from milk or mammary carcinoma cells. Eur. J. Biochem., 229, 140147.[Abstract]
Ten Hagen,K.G., Tetaert,D., Hagen,F.K., Richet,C., Beres,T.M., Gagnon,J., Balys,M.M., Van Wuyckhuyse,B., Bedi,G.S., Degand,P. and Tabak,L.A. (1999) Characterization of a UDP-GalNAc: polypeptidyl N-acetylgalactosaminyl-transferase that displays glycopeptide N-acetylgalactosyltransferase activity. J. Biol. Chem., 274, 2786727874.
Toribara,N.W., Roberton,A.M., Ho,S.B., Kuo,W.L., Gum,E., Hicks,J.W., Gum,J.R., Byrd,J.C., Siddiki,B. and Kim,Y.S (1993) Human gastric mucin. Identification of a unique species by expression cloning. J. Biol. Chem., 268, 58795885.
Treon,S.P., Mollick,J.A., Urashima,M., Teoh,G., Chauhan,D., Ogata,A., Raje,N., Hilgers,J., Nadler,L., Belch,A.R., Pilarski,L.M. and Anderson,K.C. (1999) MUC1 core protein is expressed on multiple myeloma cells and is induced by dexamethasone. Blood, 93, 12871298.
Van Klinken,B.J., Van Dijken,T.C., Oussoren,E., Buller,H.A., Dekker,J. and Einerhand,A.W. (1997) Molecular cloning of human MUC3 cDNA reveals a novel 59 amino acid tandem repeat region. Biochem. Biophys. Res. Commun., 238, 143148.[ISI][Medline]
Vavasseur,F., Yang,J.M., Dole,K., Paulsen,H. and Brockhausen,I. (1995) Synthesis of O-glycan core 3: characterization of UDP-GlcNAc: GalNAc-R ß3-N-acetylglucosaminyltransferase activity from colonic mucosal tissues and lack of the activity in human cancer cell lines. Glycobiology, 5, 351357.[Abstract]
Vinall,L.E., Hill,A.S., Pigny,P., Pratt,W.S., Toribara,N., Gum,J.R., Kim,Y.S., Porchet,N., Aubert,J.-P. and Swallow,D.M. (1998) Variable number tandem repeat polymorphism of the mucin genes located in the complex on 11p15.5. Hum. Genet., 102, 357366.[ISI][Medline]
von Mensdorff-Pouilly, Gourevitch,M.M., Kenemans,P., Verstraeten,A.A., Litvinov,S.V., van Kamp,G.J., Meijer,S., Vermorken,J. and Hilgers,J. (1996) Humoral immune response to polymorphic epithelial mucin (MUC1) in patients with benign and malignant breast tumors. Eur. J. Cancer, 32A, 13251331.
von Mensdorff-Pouilly,S., Verstraeten,A.A., Kenemans,P., Snijdewint,F.G.M., Kok,A., van Kamp,G.J., Paul,M.A., van Diest,P.J., Meijer,S. and Hilgers,J. (1999) Survival in early breast cancer patients is favourably influenced by a natural humoral immune response to polymorphic epithelial mucin (MUC1). J. Clin. Oncol., in press.
Vos,H.L., de Vries,Y. and Hilkens,J. (1991) The mouse episialin (Muc1) gene and its promoter: rapid evolution of the repetitive domain in the protein. Biochem. Biophys. Res. Commun., 181, 121130.[ISI][Medline]
Wandall,H.H., Hassan,M., Mirgorodskaya,E., Kristensen,A.K., Roepstorff,P., Bennett,E.P., Nielsen,P.A., Hollingsworth,M.A., Burchell,J., Taylor-Papadimitriou,J. and Clausen,H. (1997) Substrate specificities of three members of the human UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2 and -T3. J. Biol. Chem., 272, 2350323514.
Wesseling,J., van der Valk,S., Sonnenberg,A. and Hilkens,J. (1995) Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components. J. Cell Biol., 129, 255265.[Abstract]
Wesseling,J., van der Valk,S.W. and Hilkens,J. (1996) A mechanism for inhibition of E-cadherin-mediated cellcell adhesion by the membraneassociated mucin episialin/MUC1. Mol. Biol. Cell, 7, 565577.[Abstract]
Whitehouse,C., Burchell,J., Gschmeissner,S., Brockhausen,I., Lloyd,K.O., Taylor-Papadimitriou,J. (1997) A transfected sialyltransferase that is elevated in breast cancer and localizes to the medial/trans-Golgi apparatus inhibits the development of core-2-based O-glycans. J. Cell Biol., 137, 12291241.
Williams,S.J., McGuckin,M.A., Gotley,D.C., Eyre,H.J., Sutherland,G.R. and Antalis,T.M. (1999a) Two novel mucin genes down-regulated in colorectal cancer identified by differential display. Cancer Res., 59, 40834089.
Williams,S.J., Munster,D.J., Quin,R.J., Gotley,D.C. and McGuckin,M.A. (1999b) The MUC3 gene encodes a transmembrane mucin and is alternatively spliced. Biochem. Biophys. Res. Commun., 261, 8389.[ISI][Medline]
Wreschner,D.H., Hareuveni,M., Tsarfaty,I., Smorodinsky,N., Horev,J., Zaretzky,J., Kotkes,P., Weiss,M., Lathe,R., Dion,A. and Keydar,I. (1990) Human epithelial tumor antigen cDNA sequences. Differential splicing may generate multiple protein forms. Eur. J. Biochem., 189, 463473.[Abstract]
Yamamoto,M., Bharti,A., Li,Y. and Kufe,D. (1997) Interaction of the DF3 / MUC1 breast carcinoma-associated antigen and ß-catenin in cell adhesion. J. Biol. Chem., 272, 1249212494.
Yang,J.M., Byrd,J.C., Siddiki,B.B., Chung,Y.S., Okuno,M., Sowa,M., Kim,Y.S., Matta,K.L. and Brockhausen,I. (1994) Alterations of O-glycan biosynthesis in human colon cancer tissues. Glycobiology, 4, 873884.[Abstract]
Yolken,R.H., Peterson,J.A., Vonderfecht,S.L., Fouts,E.T., Midthun,K. and Newburg,D.S. (1992) Human milk mucin inhibits rotavirus replication and prevents experimental gastroenteritis. J. Clin. Invest., 90, 19841991.[ISI][Medline]
Zhang,K., Baeckstrom,D., Brevinge,H. and Hansson,G.C. (1996) Secreted MUC1 mucins lacking their cytoplasmic part and carrying sialyl-Lewis a andepitopes from a tumor cell line and sera of colon carcinoma patients can inhibit HL-60 leukocyte adhesion to E-selectin-expressing endothelial cells. J. Cell Biochem., 60, 538549.[ISI][Medline]
Zotter,S., Hageman,P.C., Lossnitzer,A., Mooi,W.J. and Hilgers,J. (1988) Tissue and tumor distribution of human polymorphic epithelial mucin. In Hilgers,J. and Zotter,S. (eds.), Polymorphic Epithelial Mucin and CA125-Bearing Glycoprotein As Tumor-Associated Antigens. Cancer Rev., Vol. 11/12, pp. 55101.
Zrihan-Licht,S., Vos,H.L., Baruch,A., Elroy-Stein,O., Sagiv,D., Keydar,I., Hilkens,J. and Wreschner,D. (1994) Characterization and molecular cloning of a novel MUC1 protein, devoid of tandem repeats, expressed in human breast cancer tissue. Eur. J. Biochem., 224, 787795.[Abstract]