Roger P P, Rickaert F, Lamy F, Authelet M, Dumont J E
Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, Belgium.
Exp Cell Res. 1989 May;182(1):1-13. doi: 10.1016/0014-4827(89)90274-7.
Thyrotropin (TSH), through cyclic AMP, promotes both proliferation and differentiation expression in dog thyroid epithelial cells in primary culture, whereas the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) also stimulates proliferation but antagonizes differentiating effects of TSH. In this study, within 20 min both factors triggered the disruption of actin-containing stress fibers. This process preceded distinct morphological changes: cytoplasmic retraction and arborization in response to TSH and cyclic AMP, cell shape distortion, and increased motility in response to TPA and cyclic AMP, cell shape distortion, and increased motility in response to TPA and diacylglycerol. TSH and TPA also induced a marked decrease in the synthesis of three high Mr tropomyosin isoforms, which were not present in dog thyroid tissue but appeared in culture during cell spreading and stress fiber formation. In contrast, the synthesis of two low Mr forms of tropomyosin that were already present in thyroid tissue remained unchanged after treatment with TSH or TPA. Epidermal growth factor, another mitogenic and dedifferentiating factor for these cells, did not induce acute morphological changes, nor modification of tropomyosin synthesis. The tropomyosin isoform switching observed here closely resembled similar processes in various cells transformed by oncogenic viruses. However, it did not correlate with differentiation or mitogenic activation. Contrasting with current hypothesis on this process in transformed cells, tropomyosin isoform switching in normal thyroid cells was preceded and thus might be caused by early disruption of stress fibers.
促甲状腺激素（TSH）通过环磷酸腺苷（cAMP）促进原代培养的犬甲状腺上皮细胞的增殖和分化表达，而肿瘤促进剂12 - O - 十四烷酰佛波醇13 - 乙酸酯（TPA）也刺激增殖，但拮抗TSH的分化作用。在本研究中，20分钟内这两种因子均引发了含肌动蛋白的应力纤维的破坏。这一过程先于明显的形态学变化：对TSH和cAMP的反应是细胞质收缩和分支，对TPA和cAMP的反应是细胞形状扭曲和运动性增加，对TPA和二酰基甘油的反应是细胞形状扭曲和运动性增加。TSH和TPA还导致三种高分子量原肌球蛋白同工型的合成显著减少，这些同工型在犬甲状腺组织中不存在，但在细胞铺展和应力纤维形成过程中出现在培养物中。相反，甲状腺组织中已存在的两种低分子量原肌球蛋白形式在用TSH或TPA处理后合成保持不变。表皮生长因子，这些细胞的另一种促有丝分裂和去分化因子，未诱导急性形态学变化，也未改变原肌球蛋白的合成。此处观察到的原肌球蛋白同工型转换与致癌病毒转化的各种细胞中的类似过程非常相似。然而，它与分化或有丝分裂激活无关。与目前关于转化细胞中这一过程的假设相反正常甲状腺细胞中的原肌球蛋白同工型转换先于应力纤维的早期破坏，因此可能是由应力纤维的早期破坏引起的。
