Pancreatic ductal adenocarcinomas induced in syrian hamsters by N‐nitrosobis (2‐oxopropyl) amine contain a c‐Ki‐ras oncogene with a point‐mutated codon 12

Hideki Fujii, Hiroshi Egami, William Chaney, Parviz Pour, Jill Pelling

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

We have used the polymerase chain reaction and dideoxynucleotide sequencing to amplify and sequence exons 1 and 2 of the c‐Ki‐ras proto‐oncogene from the normal Syrian golden hamster. Similar methods were employed to screen for the presence of point mutations in the c‐Ki‐ras oncogene in primary hamster pancreatic ductal adenocarcinomas (PDC) induced by N‐nitrosobis(2‐oxopropyl)amine (BOP). A GGT to GAT point mutation was detected in codon 12 of the c‐Ki‐ras gene in 10 primary hamster PDCs. This same point mutation was present in two nonclonal cell lines, PC‐1 and PC‐1‐0, established from tumors that were produced in hamsters by subcutaneously implanting a preparation of minced BOP‐induced PDC. Two clonal cell lines, CI‐3 and CI‐7, were cloned from the PC‐1 cell line, and these cell lines also carried the GAT point mutation at codon 12. This point mutation was the same as that detected in > 75% of adenocarcinomas from the human exocrine pancreas. Thus, our findings provide further validation for the use of the BOP‐induced hamster PDC model as a relevant experimental model for human pancreas cancer: not only did the hamster pancreatic ductal adenocarcinomas closely resemble their human counterpart in histopathological morphology and sequential development, but they also contained the same point mutation in codon 12 of the c‐Ki‐ras oncogene, as has been reported for human pancreatic adenocarcinomas.

Original languageEnglish (US)
Pages (from-to)296-301
Number of pages6
JournalMolecular Carcinogenesis
Volume3
Issue number5
DOIs
StatePublished - 1990

Keywords

  • Key words
  • Ki‐ras oncogene
  • Pancreas cancer
  • oncogene activation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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