PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells

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
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.
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Metadaten
Author:Sophia Boyoung Lee, Kai Doberstein, Peter Baumgarten, Anja Wieland, Christopher Ungerer, Claudia Bürger, Katja Hardt, Wolf-Henning Boehncke, Josef Martin Pfeilschifter, Daniela Mihic-Probst, Michel Guy André Mittelbronn, Paul Gutwein
URN:urn:nbn:de:hebis:30-113056
DOI:http://dx.doi.org/10.1371/journal.pone.0022312
ISSN:1932-6203
Parent Title (English):PLoS one
Document Type:Article
Language:English
Date of Publication (online):2011/08/24
Year of first Publication:2011
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2011/08/24
Note:
Copyright: © 2011 Lee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Citation: Lee SB, Doberstein K, Baumgarten P, Wieland A, Ungerer C, et al. (2011) PAX2 Regulates ADAM10 Expression and Mediates Anchorage-Independent Cell Growth of Melanoma Cells. PLoS ONE 6(8): e22312. doi:10.1371/journal.pone.0022312
Source:PLoS ONE 6(8): e22312. doi: 10.1371/journal.pone.0022312
HeBIS PPN:274739615
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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