EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1222 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)11606-11611
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number20
DOIs
StatePublished - Sep 30 2003

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells'. Together they form a unique fingerprint.

Cite this