Gustavsson B, Hermansson A, Andersson A C, Grimelius L, Bergh J, Westermark B, Heldin N E
Department of Pathology, University Hospital, Uppsala, Sweden.
Mol Cell Endocrinol. 1996 Aug 9;121(2):143-51. doi: 10.1016/0303-7207(96)03859-2.
The effect of the human TSH-receptor (TSHR) on the growth of human anaplastic thyroid carcinoma cells lacking the endogenous expression of TSHR, was studied both in vitro and in vivo in NMRI nude mice. Cells from a human anaplastic thyroid carcinoma cell line (C643) were transfected with a TSHR cDNA, and clones were isolated after neomycin selection. The expression of a functional receptor protein was ensured by analysis of the specific binding of 125I-TSH and measurement of TSH-induced cAMP. Incorporation of [3H]thymidine and increase in cell number was slightly inhibited by TSH in TSHR-expressing cells in vitro. In order to investigate whether the regained expression of a functional TSHR protein in C643 cells could influence the in vivo growth, cells were injected subcutaneously into NMRI nude mice. To manipulate the endogenous level of TSH, animals were given 6n-propyl-2-thiouracil (PTU; resulting in a high TSH level), T4 (a low TSH level) or no treatment (as a control). There seemed to be a TSH induced inhibition of tumour growth, since tumours in mice treated with PTU grew after a longer take rate and with a slower growth rate. The present results suggest a TSH-mediated growth inhibition in the TSHR-transfected C 643 anaplastic thyroid carcinoma cells.
在NMRI裸鼠体内外研究了人促甲状腺激素受体（TSHR）对缺乏内源性TSHR表达的人未分化甲状腺癌细胞生长的影响。用人促甲状腺激素受体cDNA转染人未分化甲状腺癌细胞系（C643）的细胞，经新霉素筛选后分离出克隆。通过分析125I-TSH的特异性结合和测量TSH诱导的cAMP来确保功能性受体蛋白的表达。在体外，TSH对表达TSHR的细胞中[3H]胸腺嘧啶核苷的掺入和细胞数量的增加有轻微抑制作用。为了研究C643细胞中功能性TSHR蛋白的重新表达是否会影响体内生长，将细胞皮下注射到NMRI裸鼠体内。为了控制内源性TSH水平，给动物注射6-正丙基-2-硫氧嘧啶（PTU；导致高TSH水平）、T4（低TSH水平）或不进行处理（作为对照）。似乎TSH诱导了肿瘤生长的抑制，因为用PTU处理的小鼠中的肿瘤生长起始时间更长且生长速度更慢。目前的结果表明，在转染TSHR的C643未分化甲状腺癌细胞中存在TSH介导的生长抑制作用。
