| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
The prognosis of human thyroid carcinoma are usually good, but in some case, especially poorly differentiated carcinoma are fetal. There is no good indicator which predicate the prognosis of thyroid carcinoma. In this project we found that the ras p21 protein are overexposed differentiated carcinoma and some cancer has the mutation of ras oncogene. Hepatocyte growth factor (HGF) simulated p21 protein and increased the phospholylated of Grab and PI3-kinase. In the case of differentiated thyroid carcinoma cells, HGF-induced cell motility was observed only in a low-density culture. On the other hand, in the case of poorly differentiated thyroid carcinoma cells, HGF-induced cell motility was observed not only in a low-density cultures but also in a high-density cultures. HGF increased the tyrosine phosphorylation of p125FAK,which has been shown to correlate with focal adhesion. This phosphorylation was inhibited by herbimycin A,which also blocked the cell motility response. These data suggest that HGF plays important role in the invasive phenotype of thyroid cancers. In cases of primary specimen of papillary carcinoma with recurrence, all 10 cases strongly expressed c-Met which is the receptor of HGF.Apoptosis appears to play important roles in physiological and pathological processes of the endocrine system. We showed that TSH has an inhibitory effect on apoptosis of thyroid cells via the TSH-cyclic AMP pathway and ECM regulates apoptotic cell death of malignant thyroid cells through an integrin-dependent regulation of ICE activity. It was possible that c-Met promoted cell growth and regulated the first step of oncogenesis of the thyroid. Therefore, we suggest that c-Met is a significant prognostic factor of papillary carcinoma. And is may be possible to treated the poorly differentiated thyroid carcinoma by inducing the apoptosis by HGF related signal transaction methods
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