Functional role of p66Shc in progression of human prostate cancer
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Nagasaki University|
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)
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)
|Project Period (FY)
2003 – 2004
Completed(Fiscal Year 2004)
|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)
|Keywords||prostate cancer / p66Shc / p52Shc / LNCaP cells / Tyrosine phosphorylation / androgen / ステロイドホルモン|
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.
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.
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.
Research Products (9results)