PAX transcription factors play an important role during development and
carcinogenesis. In this study, we investigated PAX2
protein levels in melanocytes and
melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of
melanoma. In vitro we found weak PAX2
protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2
protein levels were detectable in
melanoma cell lines. Interestingly, in tissue sections of
melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with
chromatin immunoprecipitation assay, PAX2 overexpression and PAX2
siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a
metalloproteinase known to play important roles in
melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign
nevi and in
melanoma cells of patients with
malignant melanoma. Importantly, the downregulation of PAX2 by specific
siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of
melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of
melanoma cells against
cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during
melanoma progression.