K‐ras and p53 Alterations in Genomic DNA and Transcripts of Human Pancreatic Adenocarcinoma Cell Lines

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 t...

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Bibliographic Details
Published in:Cancer science 1994-10, Vol.85 (10), p.1005-1014
Main Authors: Suwa, Hirofumi, Yoshimura, Tsunehiro, Yamaguchi, Nozomi, Kanehira, Kazunori, Manabe, Tadao, Imamura, Masayuki, Hiai, Hiroshi, Fukumoto, Manabu
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adenocarcinoma - genetics
Alleles
Base Sequence
Carcinogenesis
Exons
Gene deletion
Genes, p53
Genes, ras
Genomic DNA
Humans
K‐ras
Molecular Sequence Data
mRNA
Mutation
p53
p53 Protein
Pancreas
Pancreatic Neoplasms - genetics
Point Mutation
Ras protein
RNA, Messenger - analysis
Sequence Deletion
Splicing
Transcription, Genetic
Tumor cell lines
Tumor Cells, Cultured
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Summary: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, hut only TGT was transcribed into mRNA. Alterations in mRNA of the p53 gene were detected in 10 cell lines (66.7%). Analysis of the genomlc 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.
ISSN:0910-5050
1347-9032
1349-7006
1876-4673
DOI:10.1111/j.1349-7006.1994.tb02898.x