| Project/Area Number |
11671097
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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 |
Endocrinology
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| Research Institution | Tokyo Woman's Medical University |
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Principal Investigator |
TUSHIMA Toshio Tokyo women's Mea univ. Dept. of Med. Professor, 医学部, 教授 (90101089)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | thyroid cancer / MAPK / Akt / MEK / raf-1 / Bad / p70S6K / raf-1 / 甲状腺癌 / 乳頭癌 / 濾胞癌 / MAPキナーゼ |
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| Research Abstract |
Several abnormalities of oncogenes have been reported in human thyroid carcinomas. These abnormailites may be involved in molecular events leading to malignant transformation of thyroid carcinoma cells. However, a consistent or unifying pattern of activation of these protonogenes has not been seen, and there is no evidence that they are directly responsible for tumoregenesis. Clearly, events in addition to the activation of these cellular genes are important to the genesis of thyroid papillary carcinoma MAP kinase (MAPK) cascade (ras, rat-i, MEK and MAPK) and phosphoinositol 3 kinase (PI3K)-regulated kinases (PLB/Akt and p7OS6 kinase; p7OS6K) have been shown to play important roles in controlling cell proliferation. We attempted to determine if these pathways are dysregulated in human thyroid tumors. We found that both MAPK and MEK are overexpressed and constitutively activated compared to adjacent normal thyroid cells in a subset of papillary carcinomas and tollicular carcinomas. Expression of those kinases in follicular adenoma was much lower. Cancer cells also showed higher activities of p7OS6K and Akt. These findings suggest that these abnormalities are involved in uncontrolled growth of thyroid cell prolieration in a subset of thyroid cancers. Furthermore , inhibitors of the signaling pathway may be effective in treatment of thyroid cancer.
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