Activation of the insulin-like growth factor-1 receptor promotes the survival of human keratinocytes following ultraviolet B irradiation

Christine Kuhn, Steven A. Hurwitz, Manish G. Kumar, Jenny Cotton, Dan F. Spandau

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

The ultraviolet B (UVB) component of sunlight causes non-melanoma skin cancers due to the damage it inflicts on genomic DNA. The response of epidermal keratinocytes to sunlight depends on the dose of UVB received and the severity of the damage to the DNA. Mild DNA damage typically induces DNA- repair pathways and cell survival, while severe DNA damage provokes apoptosis. Primary human keratinocytes grown in serum-free media respond in a similar manner to UVB irradiation. However, we observed that keratinocytes are exquisitely more susceptible to UVB-induced apoptosis if the growth medium is depleted of exogenous growth factors. Therefore, an exogenous growth factor could provide protection from UVB-induced apoptosis. We found that the only growth factor that provided protection from UVB-induced apoptosis was insulin and that the protective effect elicited by insulin was not due to binding the insulin receptor but, rather, to activation of the insulin-like growth factor-I (IGF-1) receptor. Additionally, activation of the IGF-1 receptor in combination with UVB irradiation induced keratinocytes to become post-mitotic. This survival function of the IGF-1 receptor in response to UVB irradiation was influenced by activation of phosphatidylinositol-3 kinase and MAP kinase. Prior to UVB irradiation, insulin or IGF-1 had little to no effect on cell growth or viability. Therefore, activation of the IGF-1 receptor in conjunction with UVB irradiation promotes keratinocyte survival at the expense of cell proliferation.

Original languageEnglish (US)
Pages (from-to)431-438
Number of pages8
JournalInternational Journal of Cancer
Volume80
Issue number3
DOIs
StatePublished - Jan 13 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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