Integration of estrogen and Wnt signaling circuits by the polycomb group protein EZH2 in breast cancer cells.

Abstract:

:Essential for embryonic development, the polycomb group protein enhancer of zeste homolog 2 (EZH2) is overexpressed in breast and prostate cancers and is implicated in the growth and aggression of the tumors. The tumorigenic mechanism underlying EZH2 overexpression is largely unknown. It is believed that EZH2 exerts its biological activity as a transcription repressor. However, we report here that EZH2 functions in gene transcriptional activation in breast cancer cells. We show that EZH2 transactivates genes that are commonly targeted by estrogen and Wnt signaling pathways. We demonstrated that EZH2 physically interacts directly with estrogen receptor alpha and beta-catenin, thus connecting the estrogen and Wnt signaling circuitries, functionally enhances gene transactivation by estrogen and Wnt pathways, and phenotypically promotes cell cycle progression. In addition, we identified the transactivation activity of EZH2 in its two N-terminal domains and demonstrated that these structures serve as platforms to connect transcription factors and the Mediator complex. Our experiments indicated that EZH2 is a dual function transcription regulator with a dynamic activity, and we provide a mechanism for EZH2 in tumorigenesis.

journal_name

Mol Cell Biol

authors

Shi B,Liang J,Yang X,Wang Y,Zhao Y,Wu H,Sun L,Zhang Y,Chen Y,Li R,Zhang Y,Hong M,Shang Y

doi

10.1128/MCB.00162-07

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

5105-19

issue

14

eissn

0270-7306

issn

1098-5549

pii

MCB.00162-07

journal_volume

27

pub_type

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