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Breast Cancer Research
Published in: Breast Cancer Research 6/2008

Open Access 01-12-2008 | Research article

EZH2 and BMI1 inversely correlate with prognosis and TP53 mutation in breast cancer

Authors: Alexandra M Pietersen, Hugo M Horlings, Michael Hauptmann, Anita Langerød, Abderrahim Ajouaou, Paulien Cornelissen-Steijger, Lodewijk F Wessels, Jos Jonkers, Marc J van de Vijver, Maarten van Lohuizen

Published in: Breast Cancer Research | Issue 6/2008

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Abstract

Introduction

PolycombGroup (PcG) proteins maintain gene repression through histone modifications and have been implicated in stem cell regulation and cancer. EZH2 is part of Polycomb Repressive Complex 2 (PRC2) and trimethylates H3K27. This histone mark recruits the BMI1-containing PRC1 that silences the genes marked by PRC2. Based on their role in stem cells, EZH2 and BMI1 have been predicted to contribute to a poor outcome for cancer patients.

Methods

We have analysed the expression of EZH2 and BMI1 in a well-characterised dataset of 295 human breast cancer samples.

Results

Interestingly, although EZH2 overexpression correlates with a poor prognosis in breast cancer, BMI1 overexpression correlates with a good outcome. Although this may reflect transformation of different cell types, we also observed a functional difference. The PcG-target genes INK4A and ARF are not expressed in tumours with high BMI1, but they are expressed in tumours with EZH2 overexpression. ARF expression results in tumour protein P53 (TP53) activation, and we found a significantly higher proportion of TP53 mutations in tumours with high EZH2. This may explain why tumours with high EZH2 respond poorly to therapy, in contrast to tumours with high BMI1.

Conclusions

Overall, our data highlight that whereas EZH2 and BMI1 may function in a 'linear' pathway in normal development, their overexpression has different functional consequences for breast tumourigenesis.
Appendix
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Metadata
Title
EZH2 and BMI1 inversely correlate with prognosis and TP53 mutation in breast cancer
Authors
Alexandra M Pietersen
Hugo M Horlings
Michael Hauptmann
Anita Langerød
Abderrahim Ajouaou
Paulien Cornelissen-Steijger
Lodewijk F Wessels
Jos Jonkers
Marc J van de Vijver
Maarten van Lohuizen
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2008
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2214

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