PAX2 Regulates ADAM10 Expression and Mediates Anchorage-Independent Cell Growth of Melanoma Cells

• Published in: PloS one Vol. 6; no. 8; p. e22312
• Main Authors: Lee, Sophia Boyoung, Doberstein, Kai, Baumgarten, Peter, Wieland, Anja, Ungerer, Christopher, Bürger, Claudia, Hardt, Katja, Boehncke, Wolf-Henning, Pfeilschifter, Josef, Mihic-Probst, Daniela, Mittelbronn, Michel, Gutwein, Paul
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.08.2011; Public Library of Science (PLoS)
• Subjects: ADAM Proteins - metabolism; ADAM10 Protein; Amyloid Precursor Protein Secretases - metabolism; Analysis; Apoptosis; Biology; Carcinogenesis; Carcinogens; Cell Adhesion; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell lines; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell survival; Chemoresistance; Chromatin; Cisplatin; Cisplatin - pharmacology; Dermatology; DNA binding proteins; Down-Regulation - drug effects; Down-Regulation - genetics; Drug Resistance, Neoplasm - drug effects; Fluorescent antibody technique; Gene Knockdown Techniques; Genes; Growth; Humans; Hypoxia; Immunofluorescence; Immunohistochemistry; Immunoprecipitation; Keratinocytes; Keratinocytes - drug effects; Keratinocytes - metabolism; Keratinocytes - pathology; Medicine; Melanocytes; Melanocytes - drug effects; Melanocytes - metabolism; Melanocytes - pathology; Melanoma; Melanoma - metabolism; Melanoma - pathology; Membrane Proteins - metabolism; Metastases; Metastasis; Neoplasm Invasiveness; Neurosciences; Nevus - metabolism; Nevus - pathology; Nucleoli; Pathogenesis; Patients; Pax2 protein; PAX2 Transcription Factor - metabolism; Phenotypes; RNA, Small Interfering - metabolism; siRNA; Skin cancer; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Transcription factors; Vitiligo; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022312

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.