gms | German Medical Science

Epidemiologic and in vitro studies have shown that sunlight exposure is an etiologic agent for the development of skin cancer (1), including malignant melanoma (2). NER represents a highly conserved DNA repair pathway that removes lesions from the genome induced by UV-B exposure, such as cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts. Recently, conflicting evidence for a role of MSH2 in the transcription-coupled repair (TCR) pathway of NER has been reported (3,4). The observation that MutS homologs bind to UV light-induced photoproducts, taken together with the concept that MutS homologs influence UV-induced mutability without directly removing these UV light-induced photoproducts, has lead to the hypothesis that MMR-proteins may act as a sensor of UV-induced DNA damage, mediating a broad variety of different response mechanisms that include effects of cell cycle regulation and induction of apoptosis. It has been demonstrated that in addition to its role in error correction, MMR is required for apoptosis and G2M cell cycle arrest in response to some chemical carcinogens (5,6). The aim of this study was to investigate expression and function of the DNA MMR gene MSH2 in malignant melanoma. We asked the following questions: (i) Do we find differences in MSH2 expression comparing samples from benign acquired melanocytic nevi and malignant melanomas or metastases of malignant melanoma? (ii) Is the mRNA expression of MSH2 in melanoma cells regulated by UV-B-treatment? (iII) Do changes in MSH2-expression modulate in melanoma cells UV-B-induced effects on cell cycle or apoptosis?