ENHANCED KREV-1 EXPRESSION INHIBITS THE GROWTH OF PANCREATIC ADENOCARCINOMA CELLS

Pancreatic ductal adenocarcinoma is characterized by a high rate of ac tivating mutations involving codon 12 of the K-ras protooncogene. As a means of ras-targeted intervention, the effects of enhanced Krev-1 ge ne expression on the growth and tumorigenicity of the hamster pancreat ic adenocarcinoma cell line PC-1 were evaluated. Overexpression of the Krev-1 gene product resulted in morphologic reversion to a less trans formed phenotype, as well as retarded growth kinetics and diminished p otential for anchorage-independent growth. Among six transfected cell lines, the magnitude of these changes correlated with the degree of Kr ev-1 overexpression as assessed by Western blot. When PC-1 cells overe xpressing high levels of the Krev-1 gene product were assessed for tum origenicity in syngeneic animals, an increased latency to tumor growth and a decreased tumor size were noted. The results confirm that overe xpression of the Krev-1 gene may provide a useful strategy for ras-tar geted intervention in this disease.