A novel immediate early response gene, IEX-1, is induced by ultraviolet radiation in human keratinocytes

Skin cancer is the most common human malignancy and is strongly associated with exposure to ultraviolet radiation (UVR). Several mechanisms including an increase in immediate early gene activation have been postulated to be i nvolved in UVR-mediated carcinogenesis. We show that in a dose-dependent ma nner, WR ih-duces the expression of messenger RNA of a novel immediate earl y response gene, IEX-1, in human keratinocytes. Human keratinocytes and mou se fibroblasts transfected with an expression plasmid for IEX-1 grow at a f aster rate than keratinocytes transfected with a similar plasmid that does not contain the IEX-1 sequence. IEX-1 protein is localized predominantly in the nucleus of keratinocytes by fluorescent antibody methods and by examin ation of the location of a green fluorescence IEX-1 fusion protein. Epiderm al growth factor (EGF), a major mitogen of keratinocytes, and a tumor-promo ting phorbol ester increase IEX-1 mRNA expression. IEX-1 may play a role in keratinocyte proliferation especially following UVR. (C) 1998 Academic Pre ss.