Goldstein D R, Cacace A M, Weinstein I B
Columbia-Presbyterian Cancer Center, College of Physicians and Surgeons, Columbia University, New York 10032, USA.
Carcinogenesis. 1995 May;16(5):1121-6. doi: 10.1093/carcin/16.5.1121.
Using a retroviral vector system we have established derivatives of the E8 subclone of the human colon cancer cell line SW480 that stably overproduce a full-length rat cDNA encoding the beta 1 isoform of protein kinase C (PKC beta 1). In contrast to vectrol control cells, when treated with the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), the overexpressing cell lines displayed a striking increase in doubling time, and a decrease in saturation density. Western blot analysis indicated that treatment with TPA was also associated with translocation and partial downregulation of the exogenous PKC beta 1 in the over-expressor cell lines. These results extend previous evidence that PKC beta 1 can inhibit the growth of the HT29 human colon cancer cell line. The HT29 cells have a normal c-k-ras oncogene but the SW480 cells used in the present study have an activating mutation in this oncogene. Thus PKC beta 1 can function as a suppressor in both types of colon cancer cells.
利用逆转录病毒载体系统，我们建立了人结肠癌细胞系SW480的E8亚克隆的衍生物，这些衍生物能稳定地过量表达编码蛋白激酶C（PKCβ1）β1亚型的全长大鼠cDNA。与载体对照细胞相比，当用肿瘤启动子12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）处理时，过表达细胞系的倍增时间显著增加，饱和密度降低。蛋白质印迹分析表明，用TPA处理还与过表达细胞系中外源PKCβ1的易位和部分下调有关。这些结果扩展了先前的证据，即PKCβ1可以抑制HT29人结肠癌细胞系的生长。HT29细胞具有正常的c - k - ras癌基因，但本研究中使用的SW480细胞在该癌基因中存在激活突变。因此，PKCβ1在两种类型的结肠癌细胞中都可以作为一种抑制因子发挥作用。
