title: Histone lysine demethylases in breast cancer.
abstract: Histone lysine demethylases (KDMs) have been recently discovered in mammals and have been nicknamed "erasers" for their ability to remove methyl groups from histone substrates. In cancer cells, KDMs can activate or repress gene transcription, behaving as oncogenes or tumor suppressors depending upon the cellular context. In order to investigate the potential role of KDMs in Breast Cancer (BC), we queried the Oncomine database and determined that the expression of KDMs correlates with BC prognosis. High expression of KDM3B and KDM5A is associated with a better prognosis (no recurrence after mastectomy p=0.005 and response to docetaxel p=0.005); conversely, KDM6A is overexpressed in BC patients with an unfavorable prognosis (mortality at 1 year, p=8.65E-7). Our findings suggest that KDMs could be potential targets for BC therapy. Further, altering the interactions between KDMs and Polycomb Group genes (PcG) may provide novel avenues for therapy that specifically targets these genes in BC.
authors.affiliation: Transgenic Oncogenesis and Genomics Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute/NIH, Bethesda, MD 20892, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Paolicchi
authors.forename: Francesco
authors.initials: F
authors.lastname: Crea
authors.forename: William L
authors.initials: WL
authors.lastname: Farrar
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Green
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
mesh_terms: D001940:Breast / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000235:genetics; D030541:Databases, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000235:genetics*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D056485:Retinoblastoma-Binding Protein 2 / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C438748:KDM3B protein, human; C070050:KDM5A protein, human; C523998:KDM6A protein, human; D056485:Retinoblastoma-Binding Protein 2