%0 Journal Article
%T Integration of ER¦Á-PELP1-HER2 signaling by LSD1 (KDM1A/AOF2) offers combinatorial therapeutic opportunities to circumventing hormone resistance in breast cancer
%A Idriss M Bennani-Baiti
%J Breast Cancer Research
%D 2012
%I BioMed Central
%R 10.1186/bcr3249
%X The fact that the majority of breast cancers express estrogen receptor-alpha (ER¦Á) and thus are estrogen-dependent is both a curse and a blessing. It is a blessing because ER¦Á is a well-defined molecular target that can be efficiently inhibited by drugs in adjuvant therapy to avert relapse as well as in the palliative treatment of advanced disease. It is a curse because a significant percentage of patients fail to respond to treatment and end up relapsing. Thus, for instance, although the ER¦Á antagonist tamoxifen has proven to be one of the most successful drugs to be developed for the targeted therapy of cancer, more than half of patients with ER¦Á-positive breast cancer show intrinsic or acquired tamoxifen resistance. Therefore, the mechanisms of ER¦Á pathway drug resistance and the means of circumventing them represent high-priority fields in breast cancer research.A predominant mechanism by which ER¦Á drives breast cancer pathogenesis is the so-called nuclear genomic pathway. In this process, ER¦Á recruits co-activator complexes to gene targets to potentiate their transcription. Co-activator complexes facilitate transcriptional activation in part by interacting with chromatin remodeling and histone-modifying enzymes which render the target chromatin template permissive to transcriptional activation. One such protein is LSD1 [1], a flavin adenine dinucleotide-dependent amine oxidase that catalyzes methyl group removal from methylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) to effect transcriptional repression or activation, respectively (to avoid gene symbol and species ambiguity [2], all genes discussed in this editorial are accompanied by their unique National Center for Biotechnology Information (NCBI) GeneID: LSD1, also known as KDM1 or AOF2; GeneID 23028; encodes lysine-specific histone demethylase 1). LSD1 demethylates H3K9 of ER¦Á chromatin targets in an estrogen-dependent manner, leading to hydrogen peroxide production and recruitment of 8-oxoguanine
%U http://breast-cancer-research.com/content/14/5/112