OVEREXPRESSION OF PROTEIN-KINASE-C BETA-1 IN THE SW480 COLON-CANCER CELL-LINE CAUSES GROWTH SUPPRESSION

Using a retroviral vector system we have established derivatives of th e E8 subclone of the human colon cancer cell line SW480 that stably ov erproduce a full-length rat cDNA encoding the beta 1 isoform of protei n kinase C (PKC beta 1), In contrast to vectrol control cells, when tr eated with the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (T PA), the overexpressing cell lines displayed a striking increase in do ubling time, and a decrease in saturation density. Western blot analys is indicated that treatment with TPA was also associated with transloc ation and partial downregulation of the exogenous PKC beta 1 in the ov er-expressor cell lines. These results extend previous evidence that P KC beta 1 can inhibit the growth of the HT29 human colon cancer cell l ine, 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 oncogen e. Thus PKC beta 1 can function as a suppressor in both types of colon cancer cells.