Poster presentation, P156

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Phenotype-specific response of melanoma cells to HDAC inhibition

SPEAKER B. Belloni #whois submiter ?
AUTHOR(s) B. Belloni, P. Cheng, D. Widmer, N. Schönewolf, K.S. Hoek, R. Dummer, O. Eichhoff

Lysine-rich N-termini of Histones are subject to posttranslational modification by acetylation which leads to reduced DNA-binding properties and transcriptional activation. In turn, increased Histone deacetylase (HDAC) activity has been shown to repress transcription of genes related to differentiation, cell cycle arrest and tumor suppression in various cancer cells. There have been no detailed studies investigating the effects of HDAC inhibition on melanoma cells. We investigated the effect of the HDAC inhibitor vorinostat on different melanoma primary cultures in the context of the phenotype switching model for disease progression. Cell cultures of different phenotypes (proliferative or invasive) were treated with vorinostat in increasing concentrations (0,001 to 10 µM). After 72h a decrease in cell viability was detected only in proliferative phenotype cells which also showed apoptosis and cell cycle arrest. Furthermore, we measured the expression of cell cycle regulating genes (p15, p16, p21 and p27) in proliferative phenotype cells. After vorinostat treatment we found up-regulation of some of these tumor suppressors, suggesting that HDAC inhibitor treatment counteracts loss of cell cycle control in melanoma cells and may therefore offer a therapeutic strategy in melanoma treatment.



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Université de Bordeaux 2 & Conseil Régional Aquitaine