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Histone demethylase JMJD2B functions as a co-factor of estrogen receptor in breast cancer proliferation and mammary gland development.

Authors: Kawazu, M  Saso, K  Tong, KI  McQuire, T  Goto, K  Son, DO  Wakeham, A  Miyagishi, M  Mak, TW  Okada, H 
Citation: Kawazu M, etal., PLoS One. 2011 Mar 18;6(3):e17830. doi: 10.1371/journal.pone.0017830.
Pubmed: (View Article at PubMed) PMID:21445275
DOI: Full-text: DOI:10.1371/journal.pone.0017830

Estrogen is a key regulator of normal function of female reproductive system and plays a pivotal role in the development and progression of breast cancer. Here, we demonstrate that JMJD2B (also known as KDM4B) constitutes a key component of the estrogen signaling pathway. JMJD2B is expressed in a high proportion of human breast tumors, and that expression levels significantly correlate with estrogen receptor (ER) positivity. In addition, 17-beta-estradiol (E2) induces JMJD2B expression in an ERalpha dependent manner. JMJD2B interacts with ERalpha and components of the SWI/SNF-B chromatin remodeling complex. JMJD2B is recruited to ERalpha target sites, demethylates H3K9me3 and facilitates transcription of ER responsive genes including MYB, MYC and CCND1. As a consequence, knockdown of JMJD2B severely impairs estrogen-induced cell proliferation and the tumor formation capacity of breast cancer cells. Furthermore, Jmjd2b-deletion in mammary epithelial cells exhibits delayed mammary gland development in female mice. Taken together, these findings suggest an essential role for JMJD2B in the estrogen signaling, and identify JMJD2B as a potential therapeutic target in breast cancer.

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CRRD Object Information
CRRD ID: 9587754
Created: 2014-10-16
Species: All species
Last Modified: 2014-10-16
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.