Histone Demethylase JMJD2B Functions as a Co-Factor of Estrogen Receptor in Breast Cancer Proliferation and Mammary Gland Development

被引：155

作者：

Kawazu, Masahito ^{[1
]}

Saso, Kayoko ^{[1
]}

Tong, Kit I. ^{[1
]}

McQuire, Tracy ^{[1
]}

Goto, Kouichiro ^{[1
]}

Son, Dong-Ok ^{[1
]}

Wakeham, Andrew ^{[1
]}

Miyagishi, Makoto ^{[2
]}

Mak, Tak W. ^{[1
,3
,4
]}

Okada, Hitoshi ^{[1
,3
]}

机构：

[1] Univ Hlth Network, Ontario Canc Inst, Campbell Family Canc Res Inst, Toronto, ON, Canada

[2] Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Japan

[3] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[4] Univ Toronto, Dept Immunol, Toronto, ON, Canada

来源：

PLOS ONE | 2011年 / 6卷 / 03期

关键词：

ANDROGEN-RECEPTOR; CHROMATIN STATE; GENE-EXPRESSION; BINDING-SITES; H3; LYSINE-9; TRANSCRIPTION; GENOME; CELLS; METHYLATION; ALPHA;

D O I：

10.1371/journal.pone.0017830

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 ER alpha dependent manner. JMJD2B interacts with ER alpha and components of the SWI/SNF-B chromatin remodeling complex. JMJD2B is recruited to ER alpha 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.

引用

页数：13

共 56 条

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