TUMORIGENICITY-ASSOCIATED EXPRESSION OF PROTEIN-KINASE-C ISOFORMS IN RHABDOMYOSARCOMA-DERIVED CELLS

Cell sublines were derived from Ni-induced rat rhabdomyosarcoma which differed in their degree of tumorigenicity. We compared the expression of protein kinase C isoforms alpha, beta, gamma and epsilon in three sublines developing tumors in syngeneic rats (Sy+) and in two sublines devoid of tumorigenicity in these animals (Sy-), with that of normal skeletal muscle. Northern and Western blotting experiments showed that PKC-alpha was dramatically overexpressed in Sy- cells whereas it was underexpressed in Sy+ cells. Southern blot analysis provided evidence for a 3-fold increase of PKC alpha-related DNA fragments in Sy- cells. Steady-state levels of the PKC epsilon-related transcript were also markedly decreased in Sy+ cells. However, the expression of PKC beta-related RNA was increased in these cells. Our data support the concept that the differential expression of the PKC isoforms may play a critical role in determining the neoplastic phenotype.