Borner C, Guadagno S N, Hsieh L L, Hsiao W L, Weinstein I B
Comprehensive Cancer Center, Columbia University, New York, New York 10032.
Cell Growth Differ. 1990 Dec;1(12):653-60.
Rat embryo fibroblasts and liver epithelial cell lines normally express two isoforms of protein kinase C (PKC), PKC alpha and PKC epsilon. Derivatives of these cells transformed by an activated human c-H-ras oncogene display a several-fold increase in expression of PKC alpha and a concomitant decrease in PKC epsilon, at both the protein and mRNA levels. Similar changes are seen when the transformed phenotype is induced by Zn2+ in cells carrying the activated ras oncogene under the control of a metallothionein promoter. Studies using cell lines that express very high levels of PKC beta 1, studies using a specific inhibitor of PKC (CGP 41251), and studies in which PKC activity is down-regulated by treatment with a phorbol ester tumor promoter provide evidence that the effects of the ras oncogene on the expression of PKC alpha and PKC epsilon are mediated mainly through a PKC-independent pathway. The present results provide the first evidence that transformation of cells by an oncogene can alter the relative expression of specific isoforms of PKC. It is possible that these changes contribute to the malignant phenotype of these cells.
大鼠胚胎成纤维细胞和肝上皮细胞系通常表达蛋白激酶C（PKC）的两种同工型，即PKCα和PKCε。被激活的人c-H-ras癌基因转化的这些细胞的衍生物，在蛋白质和mRNA水平上，PKCα的表达增加了几倍，同时PKCε减少。当在金属硫蛋白启动子控制下携带激活的ras癌基因的细胞中，由Zn2+诱导转化表型时，也会出现类似的变化。使用表达非常高水平PKCβ1的细胞系的研究、使用PKC特异性抑制剂（CGP 41251）的研究，以及用佛波酯肿瘤启动子处理下调PKC活性的研究，均提供了证据表明ras癌基因对PKCα和PKCε表达的影响主要通过不依赖PKC的途径介导。目前的结果首次证明癌基因对细胞的转化可改变PKC特定同工型的相对表达。这些变化有可能促成了这些细胞的恶性表型。
