Affiliations of authors: H. Katayama, F. Suzuki, M. Tatsuka, Department of Regulatory Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Japan; T. Ota, F. Jisaki, Y. Ueda, T. Tanaka, S. Odashima, Department of Pathology, Kanazawa Medical University, Ishikawa, Japan; Y. Terada, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA.
Correspondence to: Masaaki Tatsuka, Ph.D., Department of Regulatory Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan (e-mail: haruo{at}ipc.hiroshima-u.ac.jp).
Loss of chromosomal integrity as well as genomic stability is considered to act as a driving force during the processes of tumorigenesis and tumor progression (1-3). Recently, two kinase genes involved in mitosis, the genes for aurora and IPL1-like midbody-associated protein kinase-1 (4,5) [AIM-1, registered in UniGene and also known as aurora1 (6) and ARK2 (7)] and for serine/threonine kinase-6 [STK6, also known as BTAK/STK15 (8,9), Aik (10), aurora2 (6), and ARK1 (7)], which are related to Ipl1 in Saccharomyces cerevisiae and aurora in Drosophila, have been found to be expressed at high levels in cancer cells (5,6,9). These genes encode serine/threonine protein kinases whose functional roles during chromosomal segregation processes in mitosis have been examined (4-10). In transfected human cells in vitro, the overexpression of either AIM-1 or STK6 causes chromosomal abnormalities, which are presumably attributed to a defect in the mitotic processes (5,9). Thus, these genes may be involved in the loss of chromosomal integrity during human cancer development via mitotic subversion.
Herein, we report the expression levels of these genes in human colorectal cancers of different pathologic grades. We found that both genes were highly expressed. In addition, we observed that the expression levels of AIM-1 showed a tendency to group in higher grades of malignancy defined by pathologic observation.
Fresh tumor tissues and their normal counterparts were obtained from surgically resected
specimens from 12 patients with primary colorectal cancer. Highly elevated, positive signals
were observed by in situ hybridization to AIM-1 and STK6 genes in cancerous colon as
compared with normal colon tissue (Fig. 1). These differences cannot
account for the different cell cycle progression profiles between cancerous and normal cells
because highly elevated positive signals were clearly observed during mitosis in tumors and in
cultured colon cancer cells but not in normal mitotic colon cells. Moreover, such elevated
positive signals were not detected in inflammatory cells, smooth muscle cells, endothelial cells in
the blood vessels, or other actively growing cells such as in the testis and thymus (data not
shown). Northern and western blot analyses confirmed the higher expression levels of both genes
in the tumors (Fig. 2,
a and b). The quantitation of the levels of AIM-1
and STK6 expression revealed that both genes were overexpressed in tumors, and only the
AIM-1 expression levels were increased as a function of Dukes' stage, which suggests that
AIM-1 overexpression is closely implicated in tumor progression (Fig. 2
,
c).
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NOTES
Supported by the Ministry of Education, Science, Sports and Culture of Japan; the Japan Atomic Energy Research Institute under contract to the Japanese Nuclear Safety Research Association; the Electric Technology Research Foundation of Chugoku in Japan; and the Kanazawa Medical University High-Technology Center.
H. Katayama is a student at the Graduate Department of Gene Science, Faculty of Science, Hiroshima University, Higashi-Hiroshima, Japan.
We thank H. Shimada for encouraging H. Katayama in his research.
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Manuscript received December 21, 1998; revised April 9, 1999; accepted April 24, 1999.
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