Abstract
Estrogen receptorα (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 invivo. 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.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
