Analysis of signal transduction in thyroid cancer cell

众所周知，癌细胞中发生了信号转导系统的改变。促甲状腺激素是甲状腺细胞分化和生长的主要促进因子。TSH的作用主要通过细胞内的g蛋白和c-AMP作为第二信使介导。甲状腺癌患者对TSH的反应受损。异常信号转导系统的建立可能导致恶性肿瘤细胞的选择性生长优势，从而改变细胞的生长速度。为了研究甲状腺癌细胞中信号转导受损的情况，我们对信号通路进行了研究。癌细胞与正常甲状腺细胞的TSH信号转导系统进行了比较。虽然通过测量TSH处理后c-AMP的产生和[^<-3 b> H]胸腺嘧啶掺入量证明了对牛和人TSH的无反应性，但在用福斯可林、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，^<125>I-TSH特异性结合增加，但信号转导仍然受损。这些发现提示甲状腺癌细胞对TSH无应答可能是由于TSH受体- g蛋白偶联异常或第三因子缺陷所致。

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).