K-ras and p53 alterations in genomic DNA and transcripts of human pancreatic adenocarcinoma cell lines

Hirofumi Suwa, Tsunehiro Yoshimura, Nozomi Yamaguchi, Kazunori Kanehira, Tadao Manabe, Masayuki Imamura, Hiroshi Hiai, Manabu Fukumoto

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

We analyzed 15 human pancreatic adenocarcinoma cell lines for alterations of the K-ras and the p53 genes and their transcripts. In 11 cell lines (73.3%), point mutations of the K-ras gene were found at codon 12 in exon 1. In 9 cell lines one allele was mutated and the other was wild type, and both the alleles were expressed into mRNA. In one cell line both alleles of codon 12 were mutated to TGT and GTT, respectively, but only TGT was transcribed into mRNA. Alterations in mRNA of the p53 gene were detected in 10 cell lines (66.7%). Analysis of the genomic sequence of the p53 gene revealed that the alterations consisted of 6 cases of base pair substitutions and 1 case of 1-bp deletion in evolutionarily conserved exons 5 to 8, 2 cases of splicing mutations in exon 4, and 1 case of novel deletion from exons 2 to 9. In 14 cell lines (93.3%), alterations were identified in the K-ras or p53 gene. Of these, 4 cell lines harbored K-ras mutations without p53 alteration, whereas 3 cell lines exhibited p53 alterations without K-ras mutation. Thus, it is suggested that activation of the K-ras gene and inactivation of the p53 gene are strongly and cooperatively associated with pancreatic carcinogenesis.

Original languageEnglish
Pages (from-to)1005-1014
Number of pages10
JournalJapanese Journal of Cancer Research
Volume85
Issue number10
Publication statusPublished - 1994 Oct
Externally publishedYes

Keywords

  • Genomic DNA
  • K-ras
  • mRNA
  • Mutation
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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