UNEVEN DISTRIBUTION OF PROTEIN-KINASE C-ALPHA AND C-BETA ISOZYMES IN HUMAN SARCOMAS AND CARCINOMAS

Protein kinase C (PKC) represents a family of structurally related Ser /Tre kinases which are involved in mitogenic signalling and may contri bute to human neoplasia. To address this issue, the messenger RNA and protein levels of PKC isoenzymes alpha and beta were analyzed in sever al human sarcoma- and carcinoma-derived cell lines. Carcinomas contain ed low or undetectable levels of either PKC-alpha or PKC-beta. Sarcoma s exhibited similar or increased PKC expression compared to human dipl oid fibroblasts. Moreover, sarcoma cell lines expressing one PKC isofo rm did not contain detectable levels of the other. When PKC was deplet ed from the tumor cells, we observed that the PKC overexpressing sarco mas had reduced their malignant properties as determined by their abil ity to grow in semisolid medium. In addition, epidermal growth factor- stimulated and erbB2-transformed fibroblasts exhibited enhanced cell g rowth in the absence of PKC. We propose a model for the effect of PKC as a negative regulator of proliferation in epithelial cells and a gro wth promoter in fibroblasts. (C) 1994 Wiley-Liss, Inc.