Schöfl C, Rössig L, Mader T, Börger J, Pötter E, von zur Mühlen A, Brabant G
Abteilung Klinische Endokrinologie, Medizinische Hochschule Hannover, Germany.
Mol Cell Endocrinol. 1997 Sep 30;133(1):33-9. doi: 10.1016/s0303-7207(97)00141-x.
Extracellular nucleotides like ATP that activate the Ca2+ -phosphatidylinositol (PI) signalling pathway have been suggested to participate in the regulation of normal human thyroid function. We examined, whether P2y-purinergic receptors are expressed on human thyroid cancer cells and whether post-receptor Ca2+ signalling is altered by malignant transformation. Extracellular ATP caused a biphasic increase in cytosolic free Ca2+ ([Ca2+]i) in normal human thyrocytes and in human follicular (FTC) and papillary (PTC) thyroid carcinoma cells. In FTC and PTC cell lines the dose-response curves for ATP-induced changes in [Ca2+]i were shifted to the right when compared with normal thyrocytes, whereas in undifferentiated thyroid carcinoma (UTC) cells even high concentrations of ATP (500 microM) failed to stimulate a rise in [Ca2+]i. By contrast, ATP stimulated inositol 1,4,5-trisphosphate (IP3) formation and capacitative Ca2+ entry was operational as judged by thapsigargin in normal thyrocytes and all thyroid cancer cells. Thus, P2y-purinergic receptors are expressed on thyroid tumor cells independent of degree of differentiation. In UTC cells, however, impairment in the Ca2+ -phosphatidylinositol (PI) signalling cascade occurs distal to the formation of IP3 and proximal to the activation of capacitative Ca2+ entry. Disturbed ATP-induced Ca2+ -signalling and alterations in the Ca2+ -PI signalling cascade may contribute to decreased expression or loss of specific thyroid functions in thyroid cancer cells.
像ATP这样能激活Ca2+ -磷脂酰肌醇（PI）信号通路的细胞外核苷酸，已被认为参与正常人类甲状腺功能的调节。我们研究了P2y嘌呤能受体是否在人甲状腺癌细胞上表达，以及受体后Ca2+信号是否因恶性转化而改变。细胞外ATP可使正常人甲状腺细胞、人滤泡状（FTC）和乳头状（PTC）甲状腺癌细胞中的胞质游离Ca2+（[Ca2+]i）呈双相增加。与正常甲状腺细胞相比，在FTC和PTC细胞系中，ATP诱导的[Ca2+]i变化的剂量反应曲线右移，而在未分化甲状腺癌（UTC）细胞中，即使高浓度的ATP（500微摩尔）也未能刺激[Ca2+]i升高。相比之下，ATP刺激肌醇1,4,5-三磷酸（IP3）的形成，并且毒胡萝卜素判断的钙库操纵性Ca2+内流在正常甲状腺细胞和所有甲状腺癌细胞中均起作用。因此，P2y嘌呤能受体在甲状腺肿瘤细胞上表达，与分化程度无关。然而，在UTC细胞中，Ca2+ -磷脂酰肌醇（PI）信号级联反应的损伤发生在IP3形成的远端和钙库操纵性Ca2+内流激活的近端。ATP诱导的Ca2+信号紊乱和Ca2+ -PI信号级联反应的改变可能导致甲状腺癌细胞中特定甲状腺功能的表达降低或丧失。
