Enhanced Krev-1 expression inhibits the growth of pancreatic adenocarcinoma cells.
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.
Leach
S D
SD
Department of Surgery, University of Texas-M.D. Anderson Cancer Center, Houston, USA.
Berger
D H
DH
Davidson
B S
BS
Curley
S A
SA
Tainsky
M A
MA
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D002455:Cell Division; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D008647:Mesocricetus; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D020668:rap GTP-Binding Proteins
D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins