| Project/Area Number |
08671840
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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 |
Urology
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| Research Institution | KITASATO UNIVERSITY |
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Principal Investigator |
UCHIDA Toyoaki Kitasato Univ.School of Medicine, Assistant professor, 医学部, 講師 (70146489)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMURA Masatsugu Kitasato Univ.School of Medicine, Assistant professor, 医学部, 講師 (20176564)
EGAWA Shin Kitasato Univ.School of Medicine, Assistant professor, 医学部, 講師 (60160347)
KOSHIDA Ken Kitasato Univ.School of Medicine, Professor, 医学部, 教授 (40050380)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Prostate cancer / Renal cell carcinoma / Bladder cancer / Oncogene / Tumor suppressor gene / Genomic instability / Androgen receptor |
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| Research Abstract |
We alnalysed various cancer related gene such as genomic instability using microsatellite markers, BRCA 1 gene and androgen receptor gene mutations in urogenital tumors including prostate cancer, renal cell carcinoma and bladder cancer.
Genomic instability was noted in l0-20 % of prostate cnacer, renal cell carcinoma, bladder and testicular tumors. Mutations of hMSH3, hMSH6, TGFbeta receptor type II and insulin like growth factor II receptor relating in the mismatch repair system were also identified in about 10% of mismatch repair phenotype+ (MMP+) samples but mutations of hMSH2 was not found in all cases. It may have a different pathway in development of MMP+ sporadic cancers in compare with hereditary nonpolyposis colorectal cancer. In addition, apoptotic related Bax gene was also showed mutation in MMP+ tumors.
Loss of heterozygosity (LOH) analysis on chromosome 17q21 including BRCA1 gene identified LOH in 4 of 24 (16.7%) sporadic prostate cancer and one case showed a mutation at exon 13 of the BRCA1 gene. His sister was died by ovarian cancer at 55 years old. BRCA1 gene is strongly correlated in the development in familial breast and ovarian cancer. It need further examination and longer follow up in male BRCA1 mutation carrier.
We could not any abnormality in a number of CAG repeats of the androgen receptor gene in control, benign prostaic hyperplasia and prostate cancer groups. However, one of 6 (16.7%) hormone independent prostate cancer showed a mutation of exon D of the AR gene but not of 5alpha-reductatse gene. Androgen receptor gene mutation may be related in the pathway of hormone resistance of prostate cancer.
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