Activation of the cellular Harvey ras gene in mouse skin tumors initiated with urethane

K. Bonham, T. Embry, D. Gibson, D. R. Jaffe, R. A. Roberts, Anne E Cress, G. T. Bowden

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Mouse skin tumors, benign papillomas, and squamous cell carcinomas (SCCs) were initiated by a single topical application of urethane followed by repeated promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Using the NIH 3T3 focus forming assay, dominant transforming activity was detected in DNA isolated from SCC samples. Rearranged and amplified copies of the c-Ha-ras gene were detected in NIH 3T3 transformant cell lines, indicating that an activated Ha-ras gene had been transferred to the NIH 3T3 recipient cells. Analysis of p21(ras) from the transformant cell lines suggested that the activating ras mutation was present in codon 61. Ultimately, the Ha-ras gene was shown to be activated by a specific A→T transversion at the second position of codon 61. This mutation was detected in both benign papillomas and SCCs, suggesting the activation occurred early in tumor development. The results demonstrate a highly consistent activation of the H-ras oncogene by a specific point mutation, suggesting a functional role for an activated ras gene in the initiation of mouse skin tumours by urethane.

Original languageEnglish (US)
Pages (from-to)34-39
Number of pages6
JournalMolecular Carcinogenesis
Volume2
Issue number1
StatePublished - 1989

Fingerprint

ras Genes
Urethane
Skin
Squamous Cell Carcinoma
NIH 3T3 Cells
Papilloma
Neoplasms
Codon
Proto-Oncogene Proteins p21(ras)
Cell Line
Mutation
Tetradecanoylphorbol Acetate
Point Mutation
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Bonham, K., Embry, T., Gibson, D., Jaffe, D. R., Roberts, R. A., Cress, A. E., & Bowden, G. T. (1989). Activation of the cellular Harvey ras gene in mouse skin tumors initiated with urethane. Molecular Carcinogenesis, 2(1), 34-39.

Activation of the cellular Harvey ras gene in mouse skin tumors initiated with urethane. / Bonham, K.; Embry, T.; Gibson, D.; Jaffe, D. R.; Roberts, R. A.; Cress, Anne E; Bowden, G. T.

In: Molecular Carcinogenesis, Vol. 2, No. 1, 1989, p. 34-39.

Research output: Contribution to journalArticle

Bonham, K, Embry, T, Gibson, D, Jaffe, DR, Roberts, RA, Cress, AE & Bowden, GT 1989, 'Activation of the cellular Harvey ras gene in mouse skin tumors initiated with urethane', Molecular Carcinogenesis, vol. 2, no. 1, pp. 34-39.
Bonham, K. ; Embry, T. ; Gibson, D. ; Jaffe, D. R. ; Roberts, R. A. ; Cress, Anne E ; Bowden, G. T. / Activation of the cellular Harvey ras gene in mouse skin tumors initiated with urethane. In: Molecular Carcinogenesis. 1989 ; Vol. 2, No. 1. pp. 34-39.
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