Keratinocytes exposed to ultraviolet radiation reveal three down-regulatedgenes with potential function in differentiation and cell cycle control

The incidence of skin cancer is increasing in epidemic proportion. Although solar UV radiation is known to be the major risk factor, much information is lacking about the molecular mechanisms leading to skin cancer. To gain a deeper insight into these mechanisms, we have examined cells of a human ke ratinocyte cell line (HaCat) after exposure to 0.16 minimal erythema doses of UVB radiation. This dose led to an S-phase delay that was reversible 22 h postirradiation. To examine gene expression 10 h after UV irradiation, a nonradioactive differential display was employed. Three genes were identifi ed as being down-regulated significantly. The first encodes for topoisomera se-II beta-binding protein 1 (expression level 5% 6 h after irradiation). T his protein is associated with human topoisomerase II beta and appears to b e necessary for DNA replication during the onset of S phase. The second gen e product has previously been reported to be involved in differentiation an d is therefore known as differentiation-dependent A4 protein (28% 8 h after irradiation). The third gene is XPO1 (also known as CRM1) (5% 8 h after ir radiation), whose protein is involved in nuclear export of mRNA molecules. Differential expression of these genes after UV irradiation has not been re ported. Because of their potential involvement in cell cycle control and di fferentiation, these proteins could be important for understanding the reac tion of keratinocytes after exposure to UV radiation. (C) 2000 by Radiation Research Society.