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PMID: 14500907 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 20 ·2003-09-30 ·Pages 11606-11

Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, Sabel MS, Livant D, Weiss SJ, Rubin MA, Chinnaiyan AM

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.

MeSH Terms
Breast/pathology Breast Neoplasms/metabolism,pathology Cell Transformation, Neoplastic DNA-Binding Proteins Enhancer of Zeste Homolog 2 Protein Epithelial Cells/pathology Female Humans Immunohistochemistry Polycomb Repressive Complex 2 Polymerase Chain Reaction Proteins/genetics,metabolism,physiology RNA, Messenger/genetics,metabolism Transcription Factors
Chemicals
DNA-Binding Proteins Proteins RNA, Messenger Transcription Factors EZH2 protein, human Enhancer of Zeste Homolog 2 Protein Polycomb Repressive Complex 2
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Kleer Celina G
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. kleer@umich.edu
Cao Qi
Varambally Sooryanarayana
Shen Ronglai
Ota Ichiro
Tomlins Scott A
Ghosh Debashis
Sewalt Richard G A B
Otte Arie P
Hayes Daniel F
Sabel Michael S
Livant Donna
Weiss Stephen J
Rubin Mark A
Chinnaiyan Arul M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1933744100
Email
kleer@umich.edu
Published
2003-09-30
Epub
2003-00-19
Pages
11606-11
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC208805
Subset
IM
Grants
NCI NIH HHS · P50 CA069568 · United States
NCI NIH HHS · R01 CA097063 · United States
NCI NIH HHS · P50CA69568 · United States
NCI NIH HHS · R01 CA97063 · United States
External Links
PubMed source DOI: 10.1073/pnas.1933744100 PMC Full Text View journal details
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