Enhanced Krev-1 expression inhibits the growth of pancreatic adenocarcinoma cells

Pancreas. 1998 May;16(4):491-8. doi: 10.1097/00006676-199805000-00006.

Abstract

Pancreatic ductal adenocarcinoma is characterized by a high rate of activating mutations involving codon 12 of the K-ras protooncogene. As a means of ras-targeted intervention, the effects of enhanced Krev-1 gene expression on the growth and tumorigenicity of the hamster pancreatic adenocarcinoma cell line PC-1 were evaluated. Overexpression of the Krev-1 gene product resulted in morphologic reversion to a less transformed phenotype, as well as retarded growth kinetics and diminished potential for anchorage-independent growth. Among six transfected cell lines, the magnitude of these changes correlated with the degree of Krev-1 overexpression as assessed by Western blot. When PC-1 cells overexpressing high levels of the Krev-1 gene product were assessed for tumorigenicity in syngeneic animals, an increased latency to tumor growth and a decreased tumor size were noted. The results confirm that overexpression of the Krev-1 gene may provide a useful strategy for ras-targeted intervention in this disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / pathology*
  • Animals
  • Cell Division
  • Cricetinae
  • GTP-Binding Proteins / biosynthesis*
  • Mesocricetus
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / pathology*
  • Tumor Cells, Cultured
  • rap GTP-Binding Proteins

Substances

  • GTP-Binding Proteins
  • rap GTP-Binding Proteins