A major risk factor for
skin cancer is UV irradiation, which not only damages
DNA and other photosensitive compounds like
vitamin A, but may also perturb cellular signaling, e.g. via the
retinoid receptor system believed to be important for
cancer protection. We used cultured normal human keratinocytes and melanocytes to examine the effects of UV irradiation on the expression of the predominant
retinoid receptors in the human skin (RARalpha, RARgamma and RXRalpha) and the
AP-1 protein c-Jun;
mRNA levels were studied by real-time PCR and
protein levels by Western blot. In keratinocytes, a single dose of UVB (50 mJ/cm2) caused a rapid drop in the expression of all three receptors (
mRNA levels minus 35-50% after 4 h;
protein levels minus 20-45% after 8 h), which was followed over the next 40 h by a variable response, leading to full normalization for RARalpha only. In contrast, the levels of c-Jun did not change significantly after UV exposure. In melanocytes, UVB caused a similar drop of the
retinoid receptor levels as in keratinocytes but this was soon followed by an increased expression leading to a complete normalization of all receptor levels within 1-3 days. The c-Jun levels in melanocytes increased 1 day after UV exposure and remained high (plus 50%) thereafter. In both cell types, a approximately 3-fold increase in apoptosis (measured by DNA fragmentation) was observed 8-48 h after UVB irradiation. In conclusion, a depletion of
vitamin A and
retinoid receptors by UV irradiation, together with unchanged or even increased c-Jun levels, might seriously interfere with
retinoid signaling and thus promote future
tumor development, especially in keratinocytes.