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

Celina G. Kleer | Zendy; Qi Cao | Zendy; Sooryanarayana Varambally | Zendy; Ronglai Shen | Zendy; Ichiro Ota | Zendy; Scott A. Tomlins | Zendy; Debashis Ghosh | Zendy; Richard G. A. B. Sewalt | Zendy; Arie P. Otte | Zendy; Daniel F. Hayes | Zendy; Michael S. Sabel | Zendy; Donna L. Livant | Zendy; Stephen J. Weiss | Zendy; Mark A. Rubin | Zendy; Arul M. Chinnaiyan | Zendy

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

Author(s) -

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 L. Livant,

Stephen J. Weiss,

Mark A. Rubin,

Arul M. Chinnaiyan

Publication year - 2003

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.1933744100

Subject(s) - cancer research , breast cancer , biology , ezh2 , neoplastic transformation , repressor , cancer , malignant transformation , tissue microarray , carcinogenesis , histone , transcription factor , gene , genetics

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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