| Project/Area Number |
15591696
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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 | Nagasaki University |
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Principal Investigator |
IGAWA Tsukasa Nagasaki University, Graduate School of Biomedical Sciences(Division of Nephro-Urology), Assistant, 大学院・医歯薬学総合研究科, 助手 (40295069)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Hideki Nagasaki University, Hospital of Medicine and Dentistry(Division of Nephro-Urology), Lecturer, 医学部・歯学部附属病院, 講師 (40235122)
KANETAKE Hiroshi Nagasaki University, Graduate School of Biomedical Sciences(Division of Nephro-Urology), Professor, 大学院・医歯薬学総合研究科, 教授 (50100839)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | prostate cancer / p66Shc / p52Shc / LNCaP cells / Tyrosine phosphorylation / androgen / ステロイドホルモン |
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| Research Abstract |
OBJECTIVES :
Several lines of evidence demonstrate that tyrosine phosphorylation signaling pathway has an important role in regulating androgen-responsiveness of human prostate cancer. However, the details of involvement of adaptor protein Shc remained to be elucidated. Recent studies indicate that three isoforms of Shc i.e., p52/46Shc and p66Shc exhibit distinct biological activity. Thus we analyzed the changes of Shc (especially p66 and p52Shc) and explored the biological role in human prostate cancer cells.
RESULTS :
1.Analysis of p66Shc in PCa (Prostate Cancer) cells
Among different PCa cells, the p66Shc protein level was higher in rapid-growing cells than in slow-growing cells. Stimulated proliferation by EGF (10 ng/ml) or DHT (10 nM) corresponded to elevated p66Shc protein level. Concurrently, decreased proliferation correlated with diminished p66^<Shc> protein level.
2.p66Shc expression in human prostate cancer archival specimen
Immunohistochemical analyses showed higher intensity and/or greater extent, of p66Shc protein staining in cancerous cells than that of adjacent non-cancerous cells (p<0.05).
3.p52Shc in androgen-stimulated proliferation of PCa cells
In LNCaP C-33 cells, DHT stimulation revealed the correlation with increased p-Tyr levels of p52Shc at Y317,but not at Y239,differing from the patterns associated with EGF stimulation. Moreover, over-expression of a mutant p52Shc, that is Y317F, blocks Y317 phosphorylation of endogenous p52Shc and abolishes androgen-stimulated cell proliferation but not EGF-stimulated proliferation.
CONCLUSIONS :
1.p66Shc protein levels correlate with steroid hormone-stimulated cell growth. The data thus indicates a functional role of p66Shc protein in prostate carcinogenesis, possibly by promoting PCa cell proliferation.
2.p52Shc, especially Y317 of p52Shc serves as an important regulatory site transducing androgen-responsive proliferation signals in prostate cancer cells.
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