Publication year: 2012
Source:European Journal of Cancer, Volume 48, Issue 14
Covadonga Huidobro, Rocío G. Urdinguio, Ramón María Rodríguez, Cristina Mangas, Vincenzo Calvanese, Pablo Martínez-Camblor, Cecilia Ferrero, Adolfo Parra-Blanco, Luis Rodrigo, Álvaro J. Obaya, Laura Suárez-Fernández, Aurora Astudillo, Henar Hernando, Esteban Ballestar, Agustín F. Fernández, Mario F. Fraga
Altered promoter DNA methylation, one of the most important molecular alterations in cancer, is proposed to correlate with deregulation of DNA methyltransferases, although the molecular mechanisms implicated are still poorly understood. Here we show that the de novo DNA methyltransferase DNMT3B is frequently repressed in human colorectal cancer cell lines (CCL) and primary tumours by aberrant DNA hypermethylation of its distal promoter. At the epigenome level, DNMT3B promoter hypermethylation was associated with the hypomethylation of gene promoters usually hypermethylated in the healthy colon. Forced DNMT3B overexpression in cancer cells restored the methylation levels of these promoters in the healthy colon. Our results show a new molecular mechanism of aberrant DNMT3B regulation in colon cancer and suggest that its expression is associated with the methylation of constitutively hypermethylated promoters in the healthy colon.
Júlio Leonardo B. Pereira
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