Affiliation of authors: K. Mehta, E. Devarajan, J. Chen (Department of Bioimmunotherapy), A. Multani, S. Pathak (Department of Cancer Biology), The University of Texas M. D. Anderson Cancer Center, Houston.
Correspondence to: Kapil Mehta, Ph.D., Division of Cancer Medicine, Box 422, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030 (e-mail: kmehta{at}mdanderson.org).
Two recent correspondences published in the Journal (1,2) labeled the MCF-7/ADR cell linea multidrug-resistant (MDR) human breast cancer MCF-7 sublineas having a non-MCF-7 origin, which led to a change in the nomenclature of this cell line to NCI/ADR. We believe the original nomenclature of MCF-7/ADR should be retained.
Although the two MDR MCF-7 sublines (MCF-7/ADR and MCF-7 TH) used by the investigators whose work prompted the nomenclature change were independently established, they showed several genotypic and phenotypic similarities. Both contained a full-length functional caspase-3 protein (2), despite complete loss of this protein in the parental MCF-7 cells because of a 47-base-pair deletion in exon 3 of the CASP-3 gene (3). Interestingly, several features of the MCF-7/DOX subline established in our laboratory several years ago (4) were identical to those of the MCF-7/ADR and MCF-7 TH cells but different from those of the parental MCF-7 cells (5). For example, similar to MCF-7/ADR and MCF-7 TH cells, the MCF-7/DOX cells showed high expression levels of P-glycoprotein (P-gp) and of a protein cross-linking enzyme, tissue transglutaminase; they also contained the full-length caspase-3 protein (6). We thus sought to determine whether the development of drug resistance in MCF-7 cells represents selective selection and expansion of an inherently resistant clone in the parental MCF-7 cell population. We purchased MCF-7 cells from the American Type Culture Collection (lot 2015862; Manassas, VA) and treated them with doxorubicin at 1 µg/mL. More than 99% of the MCF-7 cells died within 1 week, but a few colonies (an average of two colonies per T-75 flask were observed to grow in the presence of doxorubicin) of cells survived about 3 weeks of continuous culture in the presence of the drug. We expanded these colonies and, to our surprise, the newly established MCF-7 cell subline (MCF-7/WT/DOX) exhibited several biochemical features similar to those of the MCF-7/DOX and MCF-7/ADR cells but different from those of the parental MCF-7 cells. The MCF-7/WT/DOX cells showed high expression levels of both P-gp and tissue transglutaminase and contained full-length functional caspase-3 protein (Fig. 1, A). Karyotypic analysis of the MCF-7, MCF-7/DOX, and MCF-7/WT/DOX cell lines revealed unique features that were highly conserved in the drug-resistant sublines but were quite distinct in the parental MCF-7 cells (5).
|
Our research has demonstrated that drug-resistant MCF-7 cell lines result from parental MCF-7 cells that harbor the full-length CASP-3 gene. In view of these results, we suggest that the original nomenclature of MCF-7/ADR for MCF-7-derived drug-resistant sublines be retained to reveal the fact that various clones in a given tumor population can be extremely diverse in terms of their genotype and phenotypic characteristics.
NOTES
Editors note: Dr. Scudiero declined to comment.
REFERENCES
1 Scudiero DA, Monks A, Sausville EA. Cell line designation change: multidrug-resistant cell line in the NCI anticancer screen. J Natl Cancer Inst 1998;90:862.
2 Pirnia F, Breuleux M, Schneider E, Hochmeister M, Bates SE, Marti A, et al. Uncertain identity of doxorubicin-resistant MCF-7 cell lines expressing mutated p53. J Natl Cancer Inst 2000;92:15356.
3 Janike RU, Sprengart ML, Wati MR, Porter AG. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 1998;273:935760.
4 Mehta K. High levels of transglutaminase expression in doxorubicin-resistant human breast carcinoma cells. Int J Cancer 1994;58:4006.[Medline]
5 Devarajan E, Chen J, Multani AS, Pathak S, Sahin AA, Mehta K. Human breast cancer MCF-7 cell line contains inherently drug-resistant subclones with distinct genotypic and phenotypic features. Int J Oncol 2002;20:91320.[Medline]
6 Yang XH, Sladek TL, Liu X, Butler BR, Froelich CJ, Thor AD. Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to doxorubicin- and etoposide-induced apoptosis. Cancer Res 2001;61:34854.
7 Leoni LM, Hamel E, Genini D, Shih H, Carrera CJ, Cottam HB, et al. Indanocine, a microtubule-binding indanone and a selective inducer of apoptosis in multidrug-resistant cancer cells. J Natl Cancer Inst 2000;92:21724.
This article has been cited by other articles in HighWire Press-hosted journals:
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |