Oncogenic features of the JMJD2A histone demethylase in breast cancer

Berry,William  L.; Shin,Sook; Lightfoot,Stan  A.; Janknecht,Ralf

doi:10.3892/ijo.2012.1618

Oncogenic features of the JMJD2A histone demethylase in breast cancer

Authors:
- William L. Berry
- Sook Shin
- Stan A. Lightfoot
- Ralf Janknecht
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Affiliations: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA, Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Published online on: September 4, 2012 https://doi.org/10.3892/ijo.2012.1618
Pages: 1701-1706

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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.

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