title: Epigenetic information and estrogen receptor alpha expression in breast cancer.
abstract: In industrialized countries, breast cancer is the most common tumor in women. The tumor expression of estrogen receptors (ERs) is a very important marker for prognosis and a marker that is predictive of response to endocrine therapy. The loss of ER expression portends a poor prognosis and, in a significant fraction of breast cancers, this repression is a result of the hypermethylation of CpG islands within the ER-alpha promoter. Hypermethylation is one of the best known epigenetic events in mammalian cells. Over the last few years, many studies have found that other epigenetic events, such as deacetylation and methylation of histones, are involved in the complex mechanism that regulates promoter transcription. The exact interplay of these factors in transcriptional repression activity is not yet well understood. Inhibitors of some of these are currently being studied as new drugs able to restore ER-alpha protein expression in ER-alpha-negative breast cancer cells and to promote apoptosis and differentiation. Demethylating agents and histone deacetylase (HDAC) inhibitors are candidates for becoming potent new drugs in cancer therapy. This paper reviews the current understanding of the role of epigenetic information in the development of cancer and its significance in breast cancer as predictive markers of ER status and as new targets of anticancer therapy.
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, Pennsylvania 19122-6009, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Giacinti
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Claudio
authors.forename: Massimo
authors.initials: M
authors.lastname: Lopez
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D011379:Prognosis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D056572:Histone Deacetylase Inhibitors