Fas Gene Mutation in Pancreatic Cancer

Kim, Jin; Kim, Yoon Jun; Jang, Yoo Hyun; Lee, Woo Jin; Ryu, Ji Kon; Kim, Yong Tae; Kim, Sun Whe; Yoon, Yong Bum; Kim, Chung Yong

Abstract

BACKGROUND/AIMS: Fas is a type 1 transmembrane protein of the tumor necrosis factor (TNF) receptor superfamily, which mediates apoptosis upon cross-linking to Fas ligand. Although pancreatic cancer cells express both Fas and Fas ligand on their surface, Fas-induced apoptosis is impaired for unknown reasons. This study was performed to examine the possible role of the Fas gene mutation in the impaired Fas-mediated apoptosis in pancreatic cancer.
METHODS
From eight subjects with pancreatic cancer, needle biopsy specimens or ascites were collected and xenografted into the nude mice. After extracting genomic DNA from xenografted tumor, the entire coding region and all splice sites of the Fas gene were analyzed for the detection of the gene mutations using polymerase chain reaction-single strand conformation polymorphism method and DNA sequencing. Five pancreatic cancer cell lines were also analyzed.
RESULTS
In two-cultured cell lines of pancreatic cancer, C-to-T base change was observed in exon 7, which corresponded to the polymorphism shown in other study. No mutation resulting in amino acid substitution was observed in this study.
CONCLUSIONS
In pancreatic cancer, Fas gene mutation does not play a major role in the impairment of Fas-mediated apoptosis. Further studies focusing on downstream signalling pathways and other cofactors of apoptosis may be needed.