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Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11606-11. Epub 2003 Sep 19.

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

Author information

1
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. kleer@umich.edu

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.

PMID:
14500907
PMCID:
PMC208805
DOI:
10.1073/pnas.1933744100
[Indexed for MEDLINE]
Free PMC Article

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