Differential effects of UV irradiation on the nuclear retinoid receptor levels of cultured keratinocytes and melanocytes

• Skin cancer is the most common malignancy in man. A major risk factor is UV irradiation, which not only damages DNA 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 study the effects of UV radiation on the expression of the retinoid receptors RARα, RARβ, RARγ and RXRα. By real-time PCR and Western blot technique, the mRNA and protein levels were monitored, before and up to 4 days following 50 mJ/cm2 UVB. In keratinocytes, UVB caused a rapid drop in all four mRNA levels (minus 50-70% the first 8 h) and protein levels dropped by 30-40% followed by a gradual increase, but full normalization was ouly reached for RARα within the study period. ln melanocytes, UVB caused a quick drop both in the receptor mRNA and protein levels (minus 50-60% after 4 h), followed by normalization of the protein levels for all receptors within 2-3 days. The UV-induced depletion of vitamin A and retinoid receptors might abrogate the retinoid signaling, which subsequently might promote tumor development.

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MEDICIN

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