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EZH2 promotes a bi-lineage identity in basal-like breast cancer cells.
MedLine Citation:
PMID:  22986524     Owner:  NLM     Status:  Publisher    
The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor-associated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a 'bi-lineage' differentiation state, in which cells co-express basal- and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony-formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal-progenitor gene expression. GATA3 levels increase upon EZH2 silencing, mediating a decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition.Oncogene advance online publication, 17 September 2012; doi:10.1038/onc.2012.390.
R Z Granit; Y Gabai; T Hadar; Y Karamansha; L Liberman; I Waldhorn; I Gat-Viks; A Regev; B Maly; M Darash-Yahana; T Peretz; I Ben-Porath
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-17
Journal Detail:
Title:  Oncogene     Volume:  -     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Developmental Biology and Cancer Research, Institute for Medical Research - Israel-Canada, Hadassah School of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
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