Chen S C, Pelletier D B, Ao P, Boynton A L
Cell and Molecular Biology Department, Pacific Northwest Research Foundation, Seattle, Washington 98122, USA.
Cell Growth Differ. 1995 Jun;6(6):681-90.
Communication between adjacent cells through gap junctions is believed to be involved in the regulation of cell proliferation. This stems in part from the observation that transfection and overexpression of connexin (cx) 32 or cx43 genes into neoplastic cells lead to normalization of growth and decrease their tumorigenicity. The molecular mechanism(s) responsible for this phenomenon has not been characterized. We transfected the rat cx43 gene into a phenotypically transformed dog kidney epithelial cell line, TRMP, and were successful in restoring gap junctional communication as measured by dye coupling. In addition, cx43-transfected clones reverted to a flat morphology and were sensitive to density-dependent inhibition of proliferation with their G1 and S phase duration almost doubled. These cx43-induced effects were coupled with a decreased expression of specific cell cycle regulatory genes critical to cell cycle progression in nonneoplastic cells including cyclin A, D1, D2, and the cyclin-dependent kinases (CDK) 5 and CDK6. The protein levels of cyclin E, CDK2, and CDK4 were not affected. These results suggest that overexpression of cx43 and the formation of gap junctions with the establishment of gap junctional communication can affect the phenotype of transformed cells and alter specific gene expressions involved in cell cycle regulation.
相邻细胞间通过缝隙连接进行的通讯被认为参与细胞增殖的调控。这部分源于以下观察结果：将连接蛋白（cx）32或cx43基因转染并过表达于肿瘤细胞会导致生长正常化并降低其致瘤性。导致这种现象的分子机制尚未明确。我们将大鼠cx43基因转染到表型转化的犬肾上皮细胞系TRMP中，并通过染料偶联成功恢复了缝隙连接通讯。此外，转染cx43的克隆恢复为扁平形态，对密度依赖性增殖抑制敏感，其G1期和S期持续时间几乎加倍。这些cx43诱导的效应伴随着对非肿瘤细胞中细胞周期进展至关重要的特定细胞周期调节基因表达降低，包括细胞周期蛋白A、D1、D2以及细胞周期蛋白依赖性激酶（CDK）5和CDK6。细胞周期蛋白E、CDK2和CDK4的蛋白水平未受影响。这些结果表明，cx43的过表达以及缝隙连接的形成与缝隙连接通讯的建立可影响转化细胞的表型，并改变参与细胞周期调控的特定基因表达。
