v-ras genes from Harvey and BALB murine sarcoma viruses can act as initiators of two-stage mouse skin carcinogenesis

Cell. 1986 Aug 1;46(3):447-56. doi: 10.1016/0092-8674(86)90665-3.


Activated Harvey murine sarcoma virus ras genes were introduced into epidermal cells in vivo by direct application of retroviruses to mouse skin. Subsequent treatment with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced benign papillomas, some of which progressed to invasive carcinomas. Initiation with virus was irreversible for at least 4 months, since TPA treatment after this latency period produced papillomas within 4 weeks. Analysis of viral integration sites showed that carcinomas are clonal in origin. Both papillomas and carcinomas express virus-specific ras mRNA and the viral form of ras P21 protein. The results show that activated ras genes can replace chemical carcinogens in initiation of mouse skin carcinogenesis. This system presents a novel approach to in vivo analysis of the biological role of oncogenes in epithelial tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / analysis
  • Carcinoma / etiology*
  • Carcinoma / microbiology
  • Clone Cells / analysis
  • Cocarcinogenesis*
  • Genes, Viral*
  • Harvey murine sarcoma virus / genetics
  • Harvey murine sarcoma virus / pathogenicity
  • Mice
  • Mice, Inbred BALB C / microbiology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Oncogene Protein p21(ras)
  • Oncogenes*
  • Papilloma / analysis
  • Papilloma / etiology*
  • Papilloma / microbiology
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • RNA, Viral / analysis
  • Sarcoma Viruses, Murine / genetics*
  • Sarcoma Viruses, Murine / pathogenicity
  • Skin Neoplasms / analysis
  • Skin Neoplasms / etiology*
  • Skin Neoplasms / microbiology
  • Tetradecanoylphorbol Acetate / toxicity
  • Time Factors


  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • RNA, Viral
  • Oncogene Protein p21(ras)
  • Tetradecanoylphorbol Acetate