| Project/Area Number |
05454430
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | AKITA UNIVERSITY |
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Principal Investigator |
KATO Tetsuro Akita University, Urology, Associate professor, 医学部, 助教授 (40004642)
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| Co-Investigator(Kenkyū-buntansha) |
MORIYAMA Masatsugu Institute of Medical Science, Pathology, Assistant Tokyo University, 医科学研究所, 助手 (90239707)
SATO Kazunari Akita University, Urology, Assistant, 医学部, 助手 (90270842)
TERADA Kunihiko Akita University, Biochemistry, Assistant profesor, 医学部, 講師 (60197796)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1994: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | bladder carcinoma / c-erbB-2 / human NDF / renal cell carcinoma / HER-4 / EGFR family / urothelial carcinoma / renal cell carcinoma / heregulin / neu differentiation factor / urogenital cancer / urinary bladder cancer / renal cell cancer |
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| Research Abstract |
Expression of c-erbB-2 and human NDF gene were investigated in patients with urothelial carcinoma. Southern blot hybridization analysis demonstrated amplification of c-erbB-2 gene in 2 (6.3%) of 32 urothelial carcinomas, but neither amplification nor rearrangement of human NDF gene in the tumors. Single strand conformational polymorphism analysis (SSCP) was carried out for exon 4 to exon 9 of p53 gene to investigate whether alteration of p53 gene affected the occurrence of the amplification of c-erbB-2 gene. SSCP demonstrated 9 (28.1%) point mutations of p53 gene, while only 1 tumor have a simultaneous c-erbB-2 gene amplification, suggesting that mutation of p53 gene is not necessary for amplification of c-erbB-2 gene.
C-erbB-2 gene was overexpressed in 10 (31.0%) of 32 urothelial carcionoma, while human NDF gene was expressed in normal bladder tissue, bladder tumor and human bladder cancer cell lin (5637) in a low degree. These data suggest that occurrence and progression of urothelial carcinoma was promoted through autocrine mechanism mediated by human NDF and c-erbB-2 gene.
It has been demonstrated that a receptor type cellular membrane protein HER4 is necessary for activation of c-erbB-2 protein. Expression of human NDF,c-erbB-2 and HER4 genes was studied in 20 patients with renal cell carcinoma. Overexpression of human NDF gene was detected in only one urothelial carcinoma, while none of the tumors had overexpression of c-erbB-2 gene. HER4 gene was expressed in all normal renal tissues, but not in tumor tissues. In the tumor with overexpression of human NDF,the c-erbB-2 gene expression was lower than that in normal renal tissues. These data suggests that autocrine mechanism mediated by human NDF and c-erbB-2 genes is not necessary for proliferation and progression or renal cell carcinoma.
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