UVA-mediated activation of signaling pathways involved in skin tumor promotion and progression

Semin Cancer Biol. 2004 Apr;14(2):131-8. doi: 10.1016/j.semcancer.2003.09.017.

Abstract

Each year more than 1,000,000 cases of non-melanoma skin cancer (NMSC) are diagnosed in the Unites States. Solar radiation has been described as an important etiological factor in the development of NMSC. UVA comprises the largest portion of solar radiation reaching the surface of the earth (90-99%) and has been described to lead to benign tumor formation as well as malignant cancers, squamous cell carcinomas (SCCs). While much research has focused upon the effects of UVB radiation, little is known about UVA-induced signaling pathways and their role in tumor promotion. Here we focus on UVA-mediated activation of mitogen-activated protein kinase (MAPK) pathways and their role in activator protein-1 (AP-1) mediated transcription and cyclooxygenase-2 (COX-2) expression. AP-1 and COX-2 have been found to play a role in angiogenesis in other tissues. We propose UVA-mediated increases in AP-1 and COX-2 may play a role in tumor promotion through increases in interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). Since MAPKs, specifically p38 and JNK, appear to play a major role in the expression of UVA-induced AP-1 and COX-2, pharmacological inhibitors may be of benefit in the chemoprevention of non-melanoma skin cancer.

Publication types

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

MeSH terms

  • Cyclooxygenase 1
  • Dinoprostone / metabolism
  • Disease Progression
  • Gene Expression
  • Genes, fos
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Skin Neoplasms / etiology*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Ultraviolet Rays*
  • Up-Regulation / genetics

Substances

  • Isoenzymes
  • NF-kappa B
  • Transcription Factor AP-1
  • Cyclooxygenase 1
  • Prostaglandin-Endoperoxide Synthases
  • Mitogen-Activated Protein Kinase Kinases
  • Dinoprostone