Inhibition of erbB receptor family members protects HaCaT keratinocytes from ultraviolet-B-induced apoptosis.
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.
Lewis
Davina A
DA
Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
Zweig
Bryan
B
Hurwitz
Steven A
SA
Spandau
Dan F
DF
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000502:physiology* / Q000528:radiation effects*; D010797:Phthalimides / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D066246:ErbB Receptors; D010797:Phthalimides; D018719:Erb-b2 Receptor Tyrosine Kinases; C098874:4,5-dianilinophthalimide