Porcellini A, Ruggiano G, Pannain S, Ciullo I, Amabile G, Fenzi G, Avvedimento E V
Istituto Nazionale dei Tumori, Fondazione G Pascale, Napoli & Dipartimento di Biologia e Patologia Molecolare e Cellulare L Califano, Facoltà di Medicina, Università Federico II, Italy.
Oncogene. 1997 Aug 14;15(7):781-9. doi: 10.1038/sj.onc.1201240.
TSH receptor mutants in the VI transmembrane segment, found in thyroid autonomously functioning adeonomas, have been expressed in differentiated thyroid cells. All mutant receptors constitutively stimulated adenylyl cyclase. The biological activity, measured as cAMP production relative to the wild type receptor, was specific for each mutant in transient and stable transfection assays. Cells expressing these mutants proliferated in the absence of TSH. The rate of growth in the absence of TSH paralleled basal cAMP production for each mutant receptor. Low TSH concentrations stimulated the growth of mutant receptor-expressing cells, and not of the cells expressing the wild type receptor. Also, the entry in the cell cycle and the plating efficiency were markedly stimulated by the expression of the mutant receptors. These data provide a molecular link between the occurrence of TSH receptor mutations and thyroid autonomously functioning adenomas.
在甲状腺自主功能性腺瘤中发现的位于VI跨膜段的促甲状腺激素（TSH）受体突变体，已在分化型甲状腺细胞中表达。所有突变体受体均组成性地刺激腺苷酸环化酶。在瞬时和稳定转染实验中，以相对于野生型受体的环磷酸腺苷（cAMP）产生量来衡量的生物活性，对每个突变体都是特异性的。表达这些突变体的细胞在无TSH的情况下增殖。在无TSH时的生长速率与每个突变体受体的基础cAMP产生量平行。低浓度TSH刺激表达突变体受体的细胞生长，而不刺激表达野生型受体的细胞生长。此外，突变体受体的表达显著刺激细胞周期进入和接种效率。这些数据提供了TSH受体突变的发生与甲状腺自主功能性腺瘤之间的分子联系。
