ZNF703 gene amplification at 8p12 specifies luminal B breast cancer
Open Access
- 15 February 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 3 (3), 153-166
- https://doi.org/10.1002/emmm.201100121
Abstract
Luminal B breast cancers represent a fraction of oestrogen receptor (ER)‐positive tumours associated with poor recurrence‐free and disease‐specific survival in all adjuvant systemic treatment categories including hormone therapy alone. Identification of specific signalling pathways driving luminal B biology is paramount to improve treatment. We have studied 100 luminal breast tumours by combined analysis of genome copy number aberrations and gene expression. We show that amplification of the ZNF703 gene, located in chromosomal region 8p12, preferentially occurs in luminal B tumours. We explored the functional role of ZNF703 in luminal B tumours by overexpressing ZNF703 in the MCF7 luminal cell line. Using mass spectrometry, we identified ZNF703 as a co‐factor of a nuclear complex comprising DCAF7, PHB2 and NCOR2. ZNF703 expression results in the activation of stem cell‐related gene expression leading to an increase in cancer stem cells. Moreover, we show that ZNF703 is implicated in the regulation of ER and E2F1 transcription factor. These findings point out the prominent role of ZNF703 in transcription modulation, stem cell regulation and luminal B oncogenesis. →See accompanying Closeup by Vessela Kristensen DOI 10.1002/emmm201100128This publication has 59 references indexed in Scilit:
- ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epitheliumEMBO Molecular Medicine, 2011
- Transcription factor co‐repressors in cancer biology: roles and targetingInternational Journal of Cancer, 2010
- Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesisOncogene, 2009
- Regulation of ERBB2 by oestrogen receptor–PAX2 determines response to tamoxifenNature, 2008
- Genomic and transcriptional aberrations linked to breast cancer pathophysiologiesCancer Cell, 2006
- A collection of breast cancer cell lines for the study of functionally distinct cancer subtypesCancer Cell, 2006
- Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary glandProceedings of the National Academy of Sciences of the United States of America, 2006
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- Repeated observation of breast tumor subtypes in independent gene expression data setsProceedings of the National Academy of Sciences of the United States of America, 2003
- Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implicationsProceedings of the National Academy of Sciences of the United States of America, 2001