Document Detail


Poorly differentiated breast carcinoma is associated with increased expression of the human polycomb group EZH2 gene.
MedLine Citation:
PMID:  14965441     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polycomb group (PcG) genes contribute to the maintenance of cell identity, cell cycle regulation, and oncogenesis. We describe the expression of five PcG genes (BMI-1, RING1, HPC1, HPC2, and EZH2) innormal breast tissues, invasive breast carcinomas, and their precursors. Members of the HPC-HPH/PRC1 PcG complex, including BMI-1, RING1, HPC1, and HPC2, were detected in normal resting and cycling breast cells. The EED-EZH/PRC2 PcG complex protein EZH2 was only found in rare cycling cells, whereas normal resting breast cells were negative for EZH2. PcG gene expression patterns in ductal hyperplasia (DH), well-differentiated ductal carcinoma in situ (DCIS), and well-differentiated invasive carcinomas closely resembled the pattern in healthy cells. However, poorly differentiated DCIS and invasive carcinomas frequently expressed EZH2 in combination with HPC-HPH/PRC1 proteins. Most BMI-1/EZH2 double-positive cells in poorly differentiated DCIS were resting. Poorly differentiated invasive carcinoma displayed an enhanced rate of cell division within BMI-1/EZH2 double-positive cells. We propose that the enhanced expression of EZH2 in BMI-1(+) cells contributes to the loss of cell identity in poorly differentiated breast carcinomas, and that increased EZH2 expression precedes high frequencies of proliferation. These observations suggest that deregulated expression of EZH2 is associated with loss of differentiation and development of poorly differentiated breast cancer in humans.
Authors:
Frank M Raaphorst; Chris J L M Meijer; Elly Fieret; Tjasso Blokzijl; Ellen Mommers; Horst Buerger; Jens Packeisen; Richard A B Sewalt; Arie P Otte; Paul J van Diest
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  5     ISSN:  1522-8002     ISO Abbreviation:  Neoplasia     Publication Date:    2003 Nov-Dec
Date Detail:
Created Date:  2004-02-17     Completed Date:  2004-04-08     Revised Date:  2012-03-06    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  481-8     Citation Subset:  IM    
Affiliation:
Department of Pathology, VU University Medical Center, BioCentrum Amsterdam, University of Amsterdam, Amsterdam, The Netherlands. fm.raaphorst@vumc.nl
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MeSH Terms
Descriptor/Qualifier:
Breast / metabolism*
Breast Neoplasms / metabolism*
Carcinoma, Intraductal, Noninfiltrating / metabolism*
DNA-Binding Proteins / biosynthesis
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Neoplasm Invasiveness
Nuclear Proteins / biosynthesis
Precancerous Conditions / metabolism*
Protein Biosynthesis*
Proteins*
Proto-Oncogene Proteins / biosynthesis
Repressor Proteins*
Transcription Factors
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/EZH2 protein, human; 0/Nuclear Proteins; 0/Proteins; 0/Proto-Oncogene Proteins; 0/Repressor Proteins; 0/Transcription Factors; 138791-04-5/BMI1 protein, human; EC 6.3.2/RING1 protein, human
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