Chemoprevention of UV light-induced skin tumorigenesis by inhibition of the epidermal growth factor receptor

Taghrid B. El-Abaseri, Jill Fuhrman, Carol Trempus, Igor Shendrik, Raymond W. Tennant, Laura A. Hansen

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The epidermal growth factor receptor (EGFR) is activated in skin cells following UV irradiation, the primary cause of nonmelanoma skin cancer. The EGFR inhibitor AG1478 prevented the UV-induced activation of EGFR and of downstream signaling pathways through c-Jun NH2-terminal kinases, extracellular signal-regulated kinases, p38 kinase, and phosphatidylinositol 3-kinase in the skin. The extent to which the UV-induced activation of EGFR influences skin tumorigenesis was determined in genetically initiated v-rasHa transgenic Tg.AC mice, which have enhanced susceptibility to skin carcinogenesis. Topical treatment or i.p. injection of AG1478 before UV exposure blocked the UV-induced activation of EGFR in the skin and decreased skin tumorigenesis in Tg.AC mice. AG1478 treatment before each of several UV exposures decreased the number of papillomas arising and the growth of these tumors by ∼50% and 80%, respectively. Inhibition of EGFR suppressed proliferation, increased apoptotic cell death, and delayed the onset of epidermal hyperplasia following UV irradiation. Genetic ablation of Egfr similarly delayed epidermal hyperplasia in response to UV exposure. Thus, the UV-induced activation of EGFR promotes skin tumorigenesis by suppressing cell death, augmenting cell proliferation, and accelerating epidermal hyperplasia in response to UV. These results suggest that EGFR may be an appropriate target for the chemoprevention of UV-induced skin cancer.

Original languageEnglish (US)
Pages (from-to)3958-3965
Number of pages8
JournalCancer Research
Volume65
Issue number9
DOIs
StatePublished - May 1 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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