title: Oncogenic features of the JMJD2A histone demethylase in breast cancer.
abstract: Estrogen receptor α (ERα) plays a pivotal role in the genesis of the majority             of breast tumors. Consequently, endocrine therapy is now routinely utilized in             the clinic for the treatment of ERα-positive breast cancer patients. However,             how ERα activity becomes dysregulated in breast cancer cells remains to be elucidated.             The aim of this study was to show that the histone demethylase JMJD2A, also known             as KDM4A, is capable of forming a complex with ERα in vivo. Moreover, wild-type             JMJD2A, but not a catalytically impaired mutant, was able to strongly coactivate             ERα-mediated transcription. Consistently, the downregulation of JMJD2A in human             T47D breast cancer cells led to a decreased expression of cyclin D1, a prominent             ERα target gene and cell cycle regulator. The downregulation of JMJD2A induced             a reduction in the growth of T47D cells. In addition, we found that JMJD2A is             overexpressed in human breast tumors both at the mRNA and protein level. Taken             together, these data indicate that the overexpression of JMJD2A may contribute             to breast tumor formation by stimulating ERα activity and that JMJD2A may be a             breast-relevant oncoprotein. As such, small molecule drugs targeting the catalytic             center of JMJD2A might be useful in breast cancer adjuvant therapy.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences                     Center, Oklahoma City, OK 73104, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Berry
authors.forename: Sook
authors.initials: S
authors.lastname: Shin
authors.forename: Stan A
authors.initials: SA
authors.lastname: Lightfoot
authors.forename: Ralf
authors.initials: R
authors.lastname: Janknecht
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D014158:Transcription, Genetic
chemical_list: D047628:Estrogen Receptor alpha; D056484:Jumonji Domain-Containing Histone Demethylases; C494424:KDM4A protein, human