EZH2 is a Marker of Aggressive Breast Cancer and Promotes Neoplastic Transformation of Breast Epithelial Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Sep 23

PMID 14500907

Citations 804

Authors

Celina G Kleer

Qi Cao

Sooryanarayana Varambally

Ronglai Shen

Ichiro Ota

Scott A Tomlins

Debashis Ghosh

Richard G A B Sewalt

Arie P Otte

Daniel F Hayes

Michael S Sabel

Donna Livant

Stephen J Weiss

Mark A Rubin

Arul M Chinnaiyan

Affiliations

Soon will be listed here.

Abstract

The Polycomb Group Protein EZH2 is a transcriptional repressor involved in controlling cellular memory and has been linked to aggressive prostate cancer. Here we investigate the functional role of EZH2 in cancer cell invasion and breast cancer progression. EZH2 transcript and protein were consistently elevated in invasive breast carcinoma compared with normal breast epithelia. Tissue microarray analysis, which included 917 samples from 280 patients, demonstrated that EZH2 protein levels were strongly associated with breast cancer aggressiveness. Overexpression of EZH2 in immortalized human mammary epithelial cell lines promotes anchorage-independent growth and cell invasion. EZH2-mediated cell invasion required an intact SET domain and histone deacetylase activity. This study provides compelling evidence for a functional link between dysregulated cellular memory, transcriptional repression, and neoplastic transformation.

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