Hsiao W L, Housey G M, Johnson M D, Weinstein I B
Comprehensive Cancer Center, Columbia University, New York, New York 10032.
Mol Cell Biol. 1989 Jun;9(6):2641-7. doi: 10.1128/mcb.9.6.2641-2647.1989.
We recently developed rat fibroblast cell lines that stably overproduce high levels of the beta 1 form of protein kinase C (PKC). These cells display several disorders in growth control and form small microscopic colonies in agar. In the present study we demonstrate that one of these cell lines, R6-PKC3, is extremely susceptible to transformation by an activated human bladder cancer c-H-ras oncogene (T24). Compared with control cell line R6-C1, T24-transfected R6-PKC3 cells yielded a 10-fold increase in the formation of large colonies in agar. Cell lines established from these colonies displayed a highly transformed morphology, expressed the T24-encoded p21 ras protein, continued to express high levels of PKC, and were highly tumorigenic in nude mice. These results provide genetic evidence that PKC mediates some of the effects of the c-H-ras oncogene on cell transformation. Data are also presented suggesting that optimum synergistic effects between c-H-ras and PKC require critical levels of their respective activities. These findings may be relevant to the process of multistage carcinogenesis in tissues containing cells with an activated c-H-ras oncogene.
我们最近培育出了大鼠成纤维细胞系，这些细胞系能稳定地过量产生高水平的蛋白激酶C（PKC）的β1形式。这些细胞在生长控制方面表现出多种紊乱，并且在琼脂中形成微小的菌落。在本研究中，我们证明其中一个细胞系R6-PKC3极易被激活的人膀胱癌c-H-ras癌基因（T24）转化。与对照细胞系R6-C1相比，转染了T24的R6-PKC3细胞在琼脂中形成大菌落的数量增加了10倍。从这些菌落建立的细胞系呈现出高度转化的形态，表达T24编码的p21 ras蛋白，持续表达高水平的PKC，并且在裸鼠中具有高度致瘤性。这些结果提供了遗传学证据，表明PKC介导了c-H-ras癌基因对细胞转化的一些作用。还呈现的数据表明，c-H-ras和PKC之间的最佳协同效应需要它们各自活性的临界水平。这些发现可能与含有激活的c-H-ras癌基因的细胞的组织中的多阶段致癌过程相关。
