c-fos is required for malignant progression of skin tumors

Cell. 1995 Sep 8;82(5):721-32. doi: 10.1016/0092-8674(95)90469-7.


The proto-oncogene c-fos is a major nuclear target for signal transduction pathways involved in the regulation of cell growth, differentiation, and transformation. Using the multistep skin carcinogenesis model, we have directly tested the ability of c-fos-deficient mice to develop cancer. Upon treatment with a tumor promoter, c-fos knockout mice carrying a v-H-ras transgene were able to develop benign tumors with similar kinetics and relative incidence as wild-type animals. However, c-fos-deficient papillomas quickly became very dry and hyperkeratinized, taking on an elongated, horny appearance. While wild-type papillomas eventually progressed into malignant tumors, c-fos-deficient tumors failed to undergo malignant conversion. Experiments in which v-H-ras-expressing keratinocytes were grafted onto nude mice suggest that c-fos-deficient cells have an intrinsic defect that hinders tumorigenesis. These results demonstrate that a member of the AP-1 family of transcription factors is required for the development of a malignant tumor.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Transformation, Neoplastic / genetics
  • Epidermal Cells
  • Gene Expression / physiology
  • Genes, fos / genetics*
  • Genes, ras / genetics
  • Keratinocytes / pathology
  • Keratins / physiology
  • Mice
  • Mice, Nude
  • Mice, Transgenic
  • Mutation / physiology
  • Neoplasm Transplantation
  • Oncogene Protein p21(ras) / genetics*
  • Papilloma / genetics
  • Papilloma / pathology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Time Factors
  • Transcription Factor AP-1 / genetics


  • Transcription Factor AP-1
  • Keratins
  • Oncogene Protein p21(ras)