Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion

Mol Cell. 1999 May;3(5):565-77. doi: 10.1016/s1097-2765(00)80350-0.


The protooncogene c-myc regulates cell growth, differentiation, and apoptosis, and its aberrant expression is frequently observed in human cancer. However, the consequences of activating c-Myc in an adult tissue, in which these cellular processes are part of normal homeostasis, remain unknown. In order to achieve this, we have targeted expression of a switchable form of the c-Myc protein to the skin epidermis, a well characterized homeostatic tissue. We show that activation of c-MycER in adult suprabasal epidermis rapidly triggers proliferation and disrupts differentiation of postmitotic keratinocytes. Sustained activation of c-Myc is sufficient to induce papillomatosis together with angiogenesis--changes that resemble hyperplastic actinic keratosis, a commonly observed human precancerous epithelial lesion. All these premalignant changes spontaneously regress upon deactivation of c-MycER.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Epidermis / chemistry
  • Epidermis / metabolism*
  • Estrogen Antagonists / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hair Follicle / chemistry
  • Hair Follicle / metabolism
  • Humans
  • Hyperplasia
  • Keratinocytes / cytology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Neovascularization, Pathologic / physiopathology
  • Papilloma / genetics*
  • Papilloma / metabolism
  • Papilloma / pathology
  • Phenotype
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology


  • Estrogen Antagonists
  • Proto-Oncogene Proteins c-myc
  • Tamoxifen
  • afimoxifene