Plakoglobin is differentially expressed in alveolar and embryonal rhabdomyosarcoma and is regulated by DNA methylation and histone acetylation

Carcinogenesis
Tamara GastaldiAngelo Rosolen

Abstract

Plakoglobin (gamma-catenin) and beta-catenin are pivotal components of cell-cell adherent junctions that link cadherin receptors to the actin cytoskeleton. Whereas beta-catenin overexpression induces cell proliferation and tumor formation, plakoglobin induces tumor suppressor activity. We investigated the expression of plakoglobin in alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma (RMS) cell lines and tumors, and found that plakoglobin is present both in the cytoplasm and in the nucleus of ERMS cells, whereas it is absent or detectable at extremely low levels in ARMS. As gene silencing can be mediated by methylation and/or deacetylation of promoter regions, we assessed the effects of the DNA demethylating agent 5-Aza-2'-deoxycytidine (5AzadC) and of the histone deacetylase inhibitor Trichostatin A (TSA), and obtained restoration of plakoglobin expression in ARMS cells cultivated in the presence of 5AzadC and TSA. By methylation-specific PCR, ARMS cells were shown to contain methylated CpG dinucleotides in CpG islands located around the transcriptional start site of one or both alleles, whereas ERMS cells did not. Furthermore, we demonstrated that promoter regions (P1-P3) of plakoglobin gene were associated with hypoacetyl...Continue Reading

Citations

Aug 26, 2010·International Journal of Colorectal Disease·Jutta Maria NagelFrank Thomas Kolligs
Feb 19, 2009·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Dorothée Bouron-Dal SoglioJean-Christophe Fournet
Apr 12, 2011·Folia Histochemica Et Cytobiologica·Mirosława PüsküllüogluMarcin Majka
Sep 21, 2012·Expert Opinion on Therapeutic Targets·Mehdi H ShahiJavier S Castresana
Feb 10, 2007·Expert Review of Anticancer Therapy·Joseph G Sinkovics
May 9, 2012·Journal of Proteomics·Hee-Young YangTae-Hoon Lee
Mar 16, 2012·Epigenetics : Official Journal of the DNA Methylation Society·Sarah E MahoneyScott J Diede

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