cHa-ras proto-oncogene. Amplification and overexpression in UV-B-induced mouse skin papillomas and carcinomas

Arch Dermatol. 1990 Mar;126(3):324-30. doi: 10.1001/archderm.126.3.324.

Abstract

The role of cellular proto-oncogene activation in shortwave UV light in the B range (UV-B)--induced skin carcinogenesis was investigated. Epidermal papillomas and carcinomas were induced on the depilated skin surface of Sencar mice with single-dose UV-B irradiation (7 x 10(4) J/m2). The tumors thus initiated were present in 18.8% of treated animals and were primarily benign papillomas, while a few (6 of 17) progressed to form squamous cell carcinomas. A 5- to 10-fold stimulation of cHa-ras gene expression in both papillomas and carcinomas was observed. Other cellular proto-oncogenes such as cKi-ras, c-myc, or c-fos specific messenger RNAs were not detected in these UV-B--induced skin tumors. Subsequent Southern blot analysis revealed a threefold to fivefold amplification of cHa-ras gene in skin papillomas and carcinomas. However, only the carcinoma and not the papilloma DNA induced foci in the classic NIH-3T3 transformation assay, suggesting that activation of cHa-ras gene alone is not sufficient to exhibit this phenotypic expression of transformed cells. The NIH-3T3 transformants exhibited (1) anchorage independent growth on soft agar, (2) tumor induction in athymic mice, and (3) overexpression and amplification of the cHa-ras gene. We propose that overexpression of a ras gene by gene amplification plays a role in the UV-B--induced skin carcinogenesis process.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Carcinoma / etiology
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Line
  • DNA, Neoplasm / isolation & purification
  • Female
  • Gene Amplification* / radiation effects
  • Gene Expression / radiation effects
  • Genes, ras / physiology*
  • Genes, ras / radiation effects
  • Mice
  • Mice, Inbred Strains
  • Neoplasms, Radiation-Induced / genetics*
  • Neoplasms, Radiation-Induced / pathology
  • Papilloma / etiology
  • Papilloma / genetics*
  • Papilloma / pathology
  • Proto-Oncogene Proteins / analysis
  • RNA, Neoplasm / isolation & purification
  • Skin Neoplasms / etiology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Transfection
  • Ultraviolet Rays / adverse effects*

Substances

  • DNA, Neoplasm
  • Proto-Oncogene Proteins
  • RNA, Neoplasm