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


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.

SUBMITTER: Kleer CG 

PROVIDER: S-EPMC208805 | biostudies-literature | 2003 Sep

REPOSITORIES: biostudies-literature

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

Kleer Celina G CG   Cao Qi Q   Varambally Sooryanarayana S   Shen Ronglai R   Ota Ichiro I   Tomlins Scott A SA   Ghosh Debashis D   Sewalt Richard G A B RG   Otte Arie P AP   Hayes Daniel F DF   Sabel Michael S MS   Livant Donna D   Weiss Stephen J SJ   Rubin Mark A MA   Chinnaiyan Arul M AM  

Proceedings of the National Academy of Sciences of the United States of America 20030919 20


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 str  ...[more]

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