Multiple mechanisms of Erbb2 action after ultraviolet irradiation of the skin

Justin G. Madson, Laura A. Hansen

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Ultraviolet (UV) irradiation causes multiple pathologic changes in the skin including inflammation, immune suppression, photoaging, and cancer. Effects of UV irradiation include the activation of numerous signal transduction pathways, including the mitogen-activated protein kinases (MAPK), and the activation of transcription factors such as nuclear factor kappa B (NFκB). These responses alter gene expression in a manner that resembles the response to growth factors known as the "UV response". The UV response alters the kinetics of cell division and cell death allowing the skin to recover from the DNA damage caused by UV exposure. UV irradiation also rapidly activates epidermal growth factor receptor (EGFR) family members, including Erbb2 (human epithelial growth factor receptor 2 (HER2)/neu), through the generation of reactive oxygen species. Erbb2, a protooncogene that is activated in many types of cancer and associated with aggressive and chemotherapeutic-resistant disease, is expressed in both follicular and epidermal keratinocytes within the skin. However, the physiological functions of Erbb2 in the skin and its role in the UV response are largely unknown. In this review, evidence that Erbb2 is influential in modulating the response of the skin to UV will be presented. Erbb2 alters the expression of regulatory genes controlling inflammation, angiogenesis, cell division, apoptosis, cell adhesion, and migration following UV irradiation. In addition, Erbb2 dampens UV-induced S-phase arrest, augments inflammation in response to UV irradiation, and suppresses UV-induced apoptosis. In summary, the evidence presented herein links UV-induced Erbb2 activation to many of the effects of UV and implicates Erbb2 in UV-induced carcinogenesis.

Original languageEnglish
Pages (from-to)624-628
Number of pages5
JournalMolecular Carcinogenesis
Volume46
Issue number8
DOIs
Publication statusPublished - Aug 2007

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Molecular Biology

Cite this