Inhibition of erbB receptor family members protects HaCaT keratinocytes from ultraviolet-B-induced apoptosis

Davina A. Lewis, Bryan Zweig, Steven A. Hurwitz, Dan Spandau

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In the human epidermis, the cells most at risk for the development of cancer due to sunlight exposure are the keratinocytes. In animal models, ultraviolet-B is a complete carcinogen, capable of inducing and promoting the development of malignant cells. A key element of ultraviolet-B-induced carcinogenesis is the ability of ultraviolet-B to induce the expression of a number of cellular proteins and activate growth factor receptor tyrosine kinases, including the erbB receptor family. Keratinocytes express the erbB1 (also called EGF-R, HER1), the erbB2 (also known as neu or HER2), and the erbB3 (HER3) subtypes. In general, activation of the erbB receptor family leads to a cellular proliferative response. In certain instances, however, activation of an erbB receptor can induce differentiation, cell cycle arrest, and even apoptosis. The inhibition of tyrosine kinase activity in rodent models and human skin has been shown to inhibit some ultraviolet-B response pathways. We have shown that the inhibition of erbB receptors, by both pharmaceutical and immunologic means, will inhibit ultraviolet-B-induced apoptosis in the HaCaT human keratinocyte cell line. This inhibition was specific for the erbB receptor family and specific for ultraviolet-B-induced apoptosis. These results suggest that, in certain instances, ultraviolet-B-induced apoptotic signaling requires erbB family receptor activity.

Original languageEnglish
Pages (from-to)483-488
Number of pages6
JournalJournal of Investigative Dermatology
Volume120
Issue number3
DOIs
StatePublished - Mar 1 2003

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Keratinocytes
Apoptosis
Protein-Tyrosine Kinases
Chemical activation
Cells
Growth Factor Receptors
Aptitude
Epidermal Growth Factor
Sunlight
Carcinogens
Cell Cycle Checkpoints
Skin
Animals
Epidermis
Inhibition (Psychology)
ErbB Receptors
Rodentia
Carcinogenesis
Animal Models
Cell Line

Keywords

  • Apoptosis
  • erbB
  • Keratinocytes
  • UVB

ASJC Scopus subject areas

  • Dermatology

Cite this

Inhibition of erbB receptor family members protects HaCaT keratinocytes from ultraviolet-B-induced apoptosis. / Lewis, Davina A.; Zweig, Bryan; Hurwitz, Steven A.; Spandau, Dan.

In: Journal of Investigative Dermatology, Vol. 120, No. 3, 01.03.2003, p. 483-488.

Research output: Contribution to journalArticle

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