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Scientific article
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English

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

Contributors

Lee, Sophia Boyoung; Doberstein, Kai; Baumgarten, Peter; Wieland, Anja; Ungerer, Christopher; Burger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning; Pfeilschifter, Josef M.; Mihic-Probst, Daniela; Mittelbronn, Michel; Gutwein, Paul

Published in

PloS one, vol. 6, no. 8, e22312

Publication date

2011

Abstract

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.

Keywords

  • ADAM Proteins/*metabolism
  • Amyloid Precursor Protein Secretases/*metabolism
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Cisplatin/pharmacology
  • Down-Regulation/drug effects/genetics
  • Drug Resistance, Neoplasm/drug effects
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • Keratinocytes/drug effects/metabolism/pathology
  • Melanocytes/drug effects/metabolism/pathology
  • Melanoma/*metabolism/*pathology
  • Membrane Proteins/*metabolism
  • Neoplasm Invasiveness
  • Nevus/metabolism/pathology
  • PAX2 Transcription Factor/*metabolism
  • RNA, Small Interfering/metabolism
  • Skin Neoplasms/*metabolism/*pathology

UNIGE affiliation entities

Not a UNIGE publication

Citation (ISO format)

LEE, Sophia Boyoung et al. PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells. In: PloS one, 2011, vol. 6, n° 8, p. e22312. doi: 10.1371/journal.pone.0022312

Main files (1)

Article
CC BY

Identifiers

Additional URL for this publication

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158060/pdf/pone.0022312.pdf

Journal ISSN

1932-6203
682views
439downloads

Technical informations

Creation

20/09/2013 16:32:41

First validation

20/09/2013 16:32:41

Update

14/03/2023 20:24:34

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