Houck K A, Michalopoulos G K, Strom S C
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
Oncogene. 1989 Jan;4(1):19-25.
Growth of rat liver epithelial cells (RLEC) and primary cultures of parenchymal hepatocytes is potently inhibited by TGF-beta. Transfection of a mutated Ha-ras oncogene, but not a human c-myc oncogene, into RLEC resulted in cell lines resistant to growth inhibition by TGF-beta under anchorage-dependent conditions. Infection of primary rat hepatocyte cultures with v-Ha-ras yielded a cell line likewise insensitive to inhibition by TGF-beta. Binding of [125I]TGF-beta to Ha-ras-transfected RLEC was reduced relative to control or c-myc-transfected cells. These data suggest that activation of a Ha-ras oncogene in epithelial cells may result in escape from negative growth control and hence be a critical step during carcinogenesis. However, although Ha-ras induced resistance to growth inhibition by TGF-beta under anchorage-dependent conditions, TGF-beta inhibited the spontaneous growth in soft agar of all cell lines containing the Ha-ras oncogene. This may reflect an alteration in regulation of extracellular matrix proteins and related enzymes responsible for anchorage-independent growth.
转化生长因子-β（TGF-β）能有效抑制大鼠肝上皮细胞（RLEC）和实质肝细胞原代培养物的生长。将突变的Ha-ras癌基因而非人c-myc癌基因转染到RLEC中，可在锚定依赖条件下产生对TGF-β生长抑制有抗性的细胞系。用v-Ha-ras感染大鼠原代肝细胞培养物，也可产生同样对TGF-β抑制不敏感的细胞系。与对照或c-myc转染细胞相比，[125I]TGF-β与Ha-ras转染的RLEC的结合减少。这些数据表明，上皮细胞中Ha-ras癌基因的激活可能导致逃脱负生长控制，因此可能是致癌过程中的关键步骤。然而，尽管Ha-ras在锚定依赖条件下诱导对TGF-β生长抑制的抗性，但TGF-β抑制了所有含有Ha-ras癌基因的细胞系在软琼脂中的自发生长。这可能反映了负责非锚定依赖生长的细胞外基质蛋白和相关酶的调节发生了改变。
