Incidence of harvey ras oncogene point mutations and their expression in methylbenzylnitrosamine-induced esophageal tumorigenesis

David H. Barch*, Russell F. Jacoby, Thomas A. Brasitus, James A. Radosevich, Walter P. Carney, Philip M. Iannaccone

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Activation of the ras oncogene was investigated in esophageal tumors induced by methylbenzylnitrosarnine (MBN) in the Sprague-Dawley rat. DNA was extracted from grossly visible carcinogen-induced tumors. H-ras and K-ras gene sequences were then amplified by the polymerase chain reaction. Point mutations in the ras genes were then identified by selective hybridization to allele-specific oligonucleotide probes. A guanine to adenine transition at the 35th nucleotide in the H-ras coding sequence (GA to GA in the 12 codon) was observed in 67% (10 of 15) of the papillomas examined. This mutation codes for glutamate instead of glycine as the 12th amino acid of the ras p21 protein. No other H-ras or K-ras mutations were observed. To determine the distribution of this H-ras mutation in esophageal tissues, histological sections of MBN-treated esophagi were stained with a monoclonal antibody (E184) which selectively recognizes the mutated ras p21 with glutamate substituted for glycine as the 12th amino acid. Expression of the mutant ras p21 protein was observed in 20% of the squamous papillomas, 13.6% of hyperplastic lesions and 10 of dysplastic lesions. Thus, activation of the H-ras oncogene as a result of guanine to adenine point mutation is a frequent event in esophageal tumors induced by MBN, occurring in 67% of squamous papillomas, but expression of the corresponding mutant ras p21 protein is observed in a much smaller proportion of the tumors in this animal model.

Original languageEnglish (US)
Pages (from-to)2373-2377
Number of pages5
JournalCarcinogenesis
Volume12
Issue number12
DOIs
StatePublished - Dec 1991

ASJC Scopus subject areas

  • Cancer Research

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