Overexpression of protein kinase C beta 1 in the SW480 colon cancer cell line causes growth suppression.

Abstract

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.