2000 Fiscal Year Final Research Report Summary
Mechanism of loss of androgen dependency in prostate cancer, related to its proliferation and expansion
| Project/Area Number |
10470335
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Mie University |
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Principal Investigator |
KAWAMURA Juichi Mie University, Faculty of Medicine, Professor, 医学部, 教授 (70026839)
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| Co-Investigator(Kenkyū-buntansha) |
ARIMA Kiminobu Mie University, Hospital, Lecturer, 医学部・附属病院, 講師 (10175995)
YAMAKAWA Kensuke Mie University, Faculty of Medicine, Assistant (00230326)
HAYASHI Norio Mie University Hospital, Lecturer (70198852)
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| Project Period (FY) |
1998 – 2000
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| Keywords | prostate cancer / hormone-refractory cancer / genetic polymorphism / immunostain of Ki-67 / chromosome 8p / α6 integrin / Sp1 / MAP kinase |
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| Research Abstract |
The results of the research project are as follows :
1. Anaysis of genetic polymorphisms which may play an important role in individual susceptability with regard to prostate cancer development. 1) CYP 1A1 among catalyzing enzymes in the phase 1 and NAT1 among conjugating enzymes in the phase 2 had a significantly higher risk of prostate cancer. Moreover, combination of CYP 1 and GSTM1, one of conjugating enzyme groups, increased the risk of prostate cancer development. 2) A higher frequency of CYP 17, an enzyme gene involved in steroid metabolism, was associated with the higher risk of prostate cancer.
2. Immunohistochemical analysis using expressions of Ki-67 antigen, bc1-2 and p53 oncoproteins to predict disease progression in prostate cancer. Ki-67 labeling index was the most useful parameter to predict PSA failure or the advanced prostate cancer after the initial endocrine therapy.
3. Molecular genetic analysis of chromosome 8p in prostate cancer patients. Frequent loss of heterozygosity was observed for D8S201 (48%), LPL (48%) and DCC(26%). Microsatellite instability was observed in 28% in stages B, C and D.Unidentified genes on chromosome 8p may be involved in carcinogenesis of the prostate.
4. Investigation of mitogen-activated protein kinases (MAP kinase) pathway involving in the α6 integrin gene expression in androgen-independent prostate cancer cell lines. Sp1 consensus sequence at -48 to 43 bp from the transcription start site was necessary for basal promoter activity of the α6 integrin, suggesting that signal transduction from MAP kinases to activation of Sp1 might involved in α6 integrin expression in androgen-independent prostate cancer cell lines.
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