Journal article
DNA methylation associated with polycomb repression in retinoic acid receptor β silencing
C Moison, C Senamaud-Beaufort, L Fourrière, C Champion, A Ceccaldi, S Lacomme, A Daunay, J Tost, PB Arimondo, AL Guieysse-Peugeot
FASEB Journal | FEDERATION AMER SOC EXP BIOL | Published : 2013
DOI: 10.1096/fj.12-210971
Abstract
Retinoic acid receptor β 2 (RARβ2) is a tumor suppressor gene whose loss of expression is recurrent in prostate cancers. Here we studied the epigenetic mechanisms leading to its stable silencing. First, we characterized all RARβ isoforms in 6 human tumor cell lines (prostate DU145, LNCaP, PC3, lung A549, breast Hs578T, and colon HCT116) by RT-PCR and Western blot. We excluded loss of heterozygosity (2D-FISH) and loss of RARa expression, an upstream regulator, as origin of RARβ2 silencing. All data concluded to an epigenetic silencing. In agreement, a DNA methylation inhibitor restored its expression. Second RARβ2 loss of expression was found associated with different epigenetic profiles in L..
View full abstractGrants
Awarded by Agence Nationale de la Recherche
Funding Acknowledgements
The authors acknowledge the Service d'Anatomie et Cytologie Pathologiques des Hopitaux de Toulouse for the tumor samples. The authors thank Helene Gondelle and Jean Ollion for technical help in FISH experiments and Laurent Lacroix, Christophe Escude, Loic Ponger, and Pierre-Antoine Defossez for helpful discussions. This work was supported by Agence Nationale de la Recherche (ANR-06 JCJCJ-0080) and Region Midi-Pyrenees. C. M. was the recipient of a Ministry of Education, Research, and Technology fellowship, C. C. of an Institut National de la Sante et de la Recherche Medicale-Centre National de la Recherche Scientifique Bourse de Doctorat pour Ingenieurs, and A.C. of an ARC fellowship. The authors declare no conflicts of interest.