2000 Fiscal Year Final Research Report Summary
Regulatory Mechnism of Cyclin-dependent Kinase 2 in Uterine and Ovarian Carcinomas.
| Project/Area Number |
10671550
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | KAGAWA MEDICAL UNIVERSITY |
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Principal Investigator |
OHNO Masayuki Kagawa Medical University, Hospital, Assistant Professor, 医学部・附属病院, 講師 (40213821)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Katsuyoshi Kagawa Medical University, Physiology, Research Associate, 医学部, 助手 (80322270)
TOKUDA Masaaki Kagawa Medical University, Physiology, Professor, 医学部, 教授 (10163974)
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| Project Period (FY) |
1998 – 2000
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| Keywords | ovarian carcinomas / cell cycle / cyclin D1 / cyclin E / CDK2 / CDK4 / p27 / p16 |
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| Research Abstract |
Abnormal expression as well as interaction of cell cycle related proteins may result in malignant transformation of cells. We analyzed the expression of CDK2, CDK4, cyclin D1, cyclin E, p27kip1, and p16 in epithelial ovarian carcinomas. A panel of one hundred and three epithelial ovarian tumors was selected. Immunohistochemical staining of serial paraffin sections was performed using antibodies to these proteins. p27kip1 was expressed more frequently in benign tumors than in ovarian carcinomas. p27kip1 and cyclin D1 were concurrently expressed, and there was an inverse relationship between the expression level of these proteins and the histological tumor grades. The positive rate of cyclin E and CDK2 expression was higher in ovarian malignant tumors than that in benign tumors. The results suggest that changes in p27kip1 and cyclin D1 proteins might contribute to the dysregulation of entry of cell into S phase. Thus, reductions in p27kip1 expression appear to precede the invasive progre
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ss of ovarian tumors. Indicating that p27kip1 and cyclin D1 may be a useful prognostic marker in ovarian tumors. Cyclin E and CDK2 may concur to ovarian tumors development.
The results of immunohistochemistry showed that 60.6% and 69.7% of benign, 69.6% and 56.5% of borderline, 74.5% and 40.4% of malignant tumors expressed CDK4 and p16, respectively, demonstrating increased CDK4 and decreased p16 expression in ovarian carcinomas. There was an inverse relationship between CDK4 and p16 expression. Down-regulated p16 level was more correlated with Grade 2 and Grade 3 tumors in contrast with borderline and Grade 1 tumors. No significant relationships were observed between CDK4 and clinicopathological parameters. Western blot analysis revealed a reduced p16 expression in ovarian tumors, whereas no significant differences was observed in CDK4 expression in contrast with those in benign tumors. A significantly higher CDK4 activity was observed in malignant tumors than in benign ones. These data suggest that increased CDK4 expression and decreased p16 expression are involved in the carcinogenesis of epithelial ovarian carcinomas. Less
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