| Project/Area Number |
12213152
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Nagoya City University (2003-2004)
National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East (2000-2002) |
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Principal Investigator |
TSUDA Hiroyuki Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院医学研究科, 教授 (10163809)
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| Co-Investigator(Kenkyū-buntansha) |
高須賀 信夫 国立がんセンター研究所, 化学療法部, 主任研究官 (80270677)
國元 武彦 国立がんセンター, 化学療法部, 室長 (30072945)
飯郷 正明 国立がんセンター, 化学療法部, 室長 (80151215)
松岡 洋一郎 国立がんセンター, 化学療法部, 室長 (60219409)
内藤 暁宏 国立がんセンター, 化学療法部, 研究員 (20332372)
鳥山 弘靖 国立がんセンター, 化学療法部, 研究員 (70156537)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥43,500,000 (Direct Cost: ¥43,500,000)
Fiscal Year 2004: ¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 2003: ¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 2002: ¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 2001: ¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 2000: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Ras / transgenic rat / conditional / mammary gland / carcinogenesis / TEB / ras / 膵管発がん / 乳腺発がん / 組織発生 / 乳線発がん / 腺房 / 筋上皮 / 乳頭 / ヒトプロト型c-Ha-ras遺伝子 / 高発がん感受性 / 膀胱 / 食道 / Terminal endbud / 発がん物質中期検索法 / 皮膚 |
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| Research Abstract |
Taking the advantages of rat models characterized by larger organ size, abundant information regarding preneoplasias and virus-free constitution, we have concentrated attention on generation of transgenic rats bearing copies of the human c-Ha-ras proto-oncogene and shown the Hras 128 strain to be extremely sensitive to induction of mammary carcinomas, and to a lesser extent, lesions in the urinary bladder, esophagus and skin. In most of the mammary cancers, mutations of the transgene but not the endogenous H-ras gene are present, appearing to occur early in the process of carcinogenesis, which involves proliferation of cells in terminal end buds (TEBs) and intraductal hyperplasia before carcinomas arise. One of our recent studies demonstrated that mutation in the transgene occurred within 5 days after injection of N-methyl-N-nitrosourea and cancer development was observed within 30 days. Furthermore, while tumor development was independent of endogenous ovarian hormones, it was inhibited by soy isoflavones and promoted by atrazine and nonylphenols. Although further studies of mechanistic aspect are clearly necessary, the model appears to have great potential for screening purposes for modifying agents active in the mammary gland.
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