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Analysis of signal transduction in thyroid cancer cell

甲状腺癌细胞信号转导分析

基本信息

批准号：
04671490
负责人：
NAMBA Hiroyuki
金额：
$ 1.34万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671490/
关键词：
Thyroid cancer signal transduction 甲状腺癌

项目摘要

It is well known that the alternations of signal transduction system are occurred in cancer cell. TSH is a major differentiation and growth promoting factor to thyroid cells. The action of TSH is mainly mediated through G-protein and c-AMP as a second messenger in the cell.A response to the TSH is impaired in thyroid cancer. The establishment of an aberrant signal transduction system may lead to a selective growth advantage and change the rate of cell growth in malignancy.In order to examine the impaired signal transduction in thyroid cancer cell, we have investigated the signaling path-way. The TSH signal transduction system in the carcinoma cells was compared with that in normal thyroid cells. Although unresponsiveness to bovine and human TSH was demonstrated by measurement of c-AMP production and [^<-3>H] thymidine incorporation after treatment of TSH, c-AMP production was induced after stimulation of these cells by forskolin, Cholera toxin, and isoproterenol. Intact TSH-R overexpression in the thyroid carcinoma cell revealed that specific binding to ^<125>I-TSH was increased, but the signal transduction was still impaired.These findings suggest that the unresponsiveness to TSH in the thyroid carcinoma cells may be due to an abnormality of TSH receptor-G-protein coupling or defect of third factor(s).

众所周知，肿瘤细胞内存在着信号转导系统的改变。TSH是甲状腺细胞的主要分化和生长促进因子。TSH的作用主要通过G蛋白和作为细胞内第二信使的cAMP介导，在甲状腺癌中对TSH的反应受损。异常信号转导系统的建立可能导致选择性生长优势，改变恶性肿瘤细胞的生长速度，为了研究甲状腺癌细胞中受损的信号转导途径，我们对甲状腺癌细胞中的信号转导通路进行了研究。比较了甲状腺癌细胞和正常甲状腺细胞的TSH信号转导系统。虽然通过测量促甲状腺激素处理后c-AMP的产生和[^ H]胸苷掺入，证明了对牛和人促甲状腺激素无反应性<-3>，但在用毛喉素、霍乱毒素和异丙肾上腺素刺激这些细胞后，c-AMP的产生被诱导。甲状腺癌细胞中完整的TSH-R过表达表明，甲状腺癌细胞对TSH的特异性结合<125>增强，但信号转导仍受到损害，提示甲状腺癌细胞对TSH无反应性可能是由于TSH受体-G蛋白偶联异常或第三因子缺陷所致。