FARNESYLTRANSFERASE ACTIVITY AND MESSENGER-RNA EXPRESSION IN HUMAN SKIN BASAL-CELL CARCINOMAS

Ras oncogene encode a protein p21 which in its mutated form transforms mammalian cells only after membrane anchoring by a series of enzymati c reactions where the initial step is catalyzed by farnesyltransferase (FTase). For this reason, FTase has become an attractive target for t he development of novel anticancer agents. Virtually nothing is known about FTase activity and the association between the expression of its alpha and beta subunit genes with respect to the processing of Ras p2 1 in human cancers. In this study, we found that compared to normal sk in, FTase activity and levels of both cytosolic and membrane-bound Ha- Ras p21 were significantly higher in human skin basal cell carcinomas (BCCs). In addition, the expression of both alpha and beta subunit gen es was significantly higher in BCCs than the normal skin. These result s suggest an association between enhanced FTase activity and the proce ssing of overexpressed Ras p21 in such tumor type. This may have a bea ring on the pathogenesis of activated Ras oncogene containing human ma lignancies. (C) 1996 Academic Press, Inc.