| Co-Investigator(Kenkyū-buntansha) |
SOEJIMA Mikiko KURUME UNIVERSITY, Department of Medicine, Assistant, 医学部, 助手 (80279140)
KODA Yoshiro KURUME UNIVERSITY, Department of Medicine, Professor, 医学部, 教授 (90231307)
KIMURA Hiroshi KURUME UNIVERSITY, Department of Medicine, Professor, 医学部, 教授 (20112039)
TEYE Kwesi KURUME UNIVERSITY, Department of Medicine, Assistant, 医学部, 助手 (80352128)
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| Research Abstract |
Myc is a ubiquitous mediator of cell proliferation and transactivates the expressions of genes through E-box sites. Although much effort has been made to investigate myc, myc still remains enigmatic, and information about additional genes controlled by myc can help elucidate the function of Myc.
We found a novel gene, mina53 (myc-induced nuclear antigen with a MW of 53 kDa). The changes of the expression level of mina53 followed those of c-myc in various types of cells. When, c-Myc in the c-MycER chimeric protein was activated, mina53 mRNA was increased, even in the presence of an inhibitor for protein synthesis. c-Myc protein bound to the mina53 promoter region in vivo. The gene expression from the mina53 promoter was elevated by c-Myc through an E-box site in the mina53 promoter. Specific inhibition of mina53 expression by an RNA interference method severely suppressed cell proliferation. These results indicate that mina53 is a direct target gene of Myc, and suggest that mina53 is involved in mammalian cell proliferation.
We generated a specific monoclonal anti-human Mina53 antibody and found that colon tumor cell lines expressed Mina53 highly. Then, we studied the expression of Mina53 in colon cancer to examine its possible role in carcinogenesis. Tissue sections of adenocarcinoma were stained immunohistochemically, and the expression of Mina53 was found to be elevated in all the adenocarcinomas compared to adjacent non-neoplastic tissues. Mina53 was expressed in all pathological grades of cancer as well as in the adenoma. Staining patterns of Ki-67, a biomarker for cell proliferation, were similar to those of Mina53 in most cases. While anti-Ki-67 antibody strongly stained cells in lymphoid germinal centers, however, antibody to Mina53 rarely stained those cells. Together, our results indicate that the elevated expression of Mina53 is a characteristic feature in colon cancer, one that may have therapeutic applications.
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