Oncogenic features of the JMJD2A histone demethylase in breast cancer.
作者： WILLIAM L. BERRY , SOOK SHIN , STAN A. LIGHTFOOT , RALF JANKNECHT
关键词: Adjuvant therapy 、 Breast cancer 、 Downregulation and upregulation 、 Cancer research 、 Estrogen receptor 、 Cyclin D1 、 Biology 、 Cell cycle 、 Demethylase 、 Oncogene
摘要: Estrogen receptor α (ERα) plays a pivotal role in the genesis of majority breast tumors. Consequently, endocrine therapy is now routinely utilized clinic for treatment ERα-positive cancer patients. However, how ERα activity becomes dysregulated cells remains to be elucidated. The aim this study was show that histone demethylase JMJD2A, also known as KDM4A, capable forming complex with in vivo. Moreover, wild-type but not catalytically impaired mutant, able strongly coactivate ERα-mediated transcription. Consistently, downregulation JMJD2A human T47D led decreased expression cyclin D1, prominent target gene and cell cycle regulator. induced reduction growth cells. In addition, we found overexpressed tumors both at mRNA protein level. Taken together, these data indicate overexpression may contribute tumor formation by stimulating breast-relevant oncoprotein. As such, small molecule drugs targeting catalytic center might useful adjuvant therapy.
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