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Nat Commun. 2015 Jan 9;6:5987. doi: 10.1038/ncomms6987.

BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells.

Author information

1
1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK [2] Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK [3].
2
1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK [2].
3
Cancer Research UK Cambridge Institute, and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
4
SAIC-Frederic, National Cancer Institute-Frederick, Frederick, Maryland 21701, USA.
5
1] Cancer Research UK Cambridge Institute, and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK [2] Cambridge Experimental Cancer Medicine Centre, Cambridge CB2 0RE, UK.
6
Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
7
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK.
8
The Methodist Hospital Research Institute, 6670 Bertner Street, Houston, Texas 77030, USA.
9
Molecular Oncology Department, BC Cancer Agency Research Centre, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
10
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
11
1] Cancer Research UK Cambridge Institute, and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK [2] Cambridge Experimental Cancer Medicine Centre, Cambridge CB2 0RE, UK [3] Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 2QQ, UK.

Abstract

Triple-negative breast cancer (TNBC) has poor prognostic outcome compared with other types of breast cancer. The molecular and cellular mechanisms underlying TNBC pathology are not fully understood. Here, we report that the transcription factor BCL11A is overexpressed in TNBC including basal-like breast cancer (BLBC) and that its genomic locus is amplified in up to 38% of BLBC tumours. Exogenous BCL11A overexpression promotes tumour formation, whereas its knockdown in TNBC cell lines suppresses their tumourigenic potential in xenograft models. In the DMBA-induced tumour model, Bcl11a deletion substantially decreases tumour formation, even in p53-null cells and inactivation of Bcl11a in established tumours causes their regression. At the cellular level, Bcl11a deletion causes a reduction in the number of mammary epithelial stem and progenitor cells. Thus, BCL11A has an important role in TNBC and normal mammary epithelial cells. This study highlights the importance of further investigation of BCL11A in TNBC-targeted therapies.

PMID:
25574598
PMCID:
PMC4338552
DOI:
10.1038/ncomms6987
[Indexed for MEDLINE]
Free PMC Article

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