Role of apoptosis in basal cell and squamous cell carcinoma formation

Immunol Lett. 2005 Aug 15;100(1):68-72. doi: 10.1016/j.imlet.2005.06.008.


Long-term ultraviolet-light (UV) exposure of human skin epidermis is associated with an increased risk for the development of skin cancers, such as melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). UV radiation not only induces DNA damage in epidermal cells, it also interferes with skin homeostasis, which is maintained by a unique distribution pattern of apoptosis-inducing and -preventing molecules. If the DNA damage is not repaired or the damaged cells are not eliminated by apoptosis, the consequence can be cell transformation, uncontrolled proliferation and eventually skin tumor formation. An important "repair" gene is the p53 suppressor gene. Excessive UV exposure can mutate the p53 gene leading to the loss of its repair function and thus apoptosis resistance of the DNA-damaged cell. For BCC formation an additional pathway has been identified. Mutation of genes of the Hedgehog signaling pathway evokes the downregulation of apoptotic genes and upregulation of anti-apoptotic genes preventing the elimination of damaged cells. In addition, BCC and SCC strongly express the apoptosis-inducing Fas-ligand (FasL) which may help the tumor to escape the attack of immune effector cells. Silencing the genes involved in tumor formation by RNA interference might become a promising new approach to treat skin tumors.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis* / genetics
  • Carcinoma, Basal Cell / genetics
  • Carcinoma, Basal Cell / metabolism*
  • Carcinoma, Basal Cell / therapy
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / therapy
  • DNA Damage / genetics
  • DNA Damage / radiation effects
  • Fas Ligand Protein
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / radiation effects*
  • Hedgehog Proteins
  • Humans
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Mice
  • Mutation
  • Signal Transduction / genetics
  • Signal Transduction / radiation effects*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / therapy
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ultraviolet Rays / adverse effects*


  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Hedgehog Proteins
  • Membrane Glycoproteins
  • Trans-Activators
  • Tumor Suppressor Protein p53