2005 Fiscal Year Final Research Report Summary
Role of Cdc25 protein in hormone refractory prostate cancer
| Project/Area Number |
16591626
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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 | Nippon Medical School |
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Principal Investigator |
NISHIMURA Taiji Nippon Medical School, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (00104026)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Yukihiro Nippon Medical School, Department of Medicine, Associate Professor, 医学部, 助教授 (80215467)
NEMOTO Kaoru Nippon Medical School, Department of Medicine, Research Associate, 医学部, 助手 (90328823)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Prostate cancer / Androgen response / EGF receptor / Cdc 25 |
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| Research Abstract |
BACKGROUND : The serine/threonine kinase Raf-1 is a major regulator of the mitogen activated protein kinase (MAPK) pathway, which has been associated with the progression of prostate cancer to the more advanced and androgen-independent disease. Cdc25A phosphatase has been implicated in the regulation of Raf-1 and the MAPK pathway. METHODS : We used a novel and potent Cdc25A inhibitor, 2,3-bis-[2-hydroxyethylsulfonyl]-[1,4] naphthoquinone (NSC 95397), and its congener (2-mercaptoethanol)-3-methyl-1,4-naphthoquinone (NSC 672121) to study the role of Cdc25A on the MAPK pathway in human prostate cancer cells. RESULTS : We found Raf-1 physically interacted with Cdc25A in PC-3 and LNCap cells and inhibitors of Cdc25A induced both extracellular signal-regulated kinase (Erk) activation and Raf-1 tyrosine phosphorylation. NSC 95397 attenuated Cdc25A and Raf-1 interactions due to accelerated degradation of Cdc25A, which was mediated by proteasome degradation. The MAPK kinase (MEK) inhibitor U0126 completely inhibited Erk activation by NSC 95397 and NSC 672121. CONCLUSIONS : These results indicate Cdc25A phosphatase regulates Raf-1/MEK/Erk kinase activation in human prostate cancer cells.
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[Journal Article] Nucleotide variations in genes encoding plasminogen activator inhibitor-2 and serine prosteinase inhibitor B10 associated with prostate cancer.2005
Author(s)
Shioji Go, Ezura Yoichi, Nakajima Toshiaki, Ohgaki Kenji, Fujiwara Hiromichi, Kubota Yoshinobu, Ichikawa Tomohiko, Inoue Katsuki, Shuin Taro, Habuchi Tomonori, Ogawa Osamu, Nishimura Taiji, Emi Mitsuru
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Journal Title
J Hum.Genet 50
Pages: 507-515
Description
「研究成果報告書概要(欧文)」より
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