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E-GEOD-63386 - BCL11A: A Novel Breast Cancer Gene which Plays a Critical Role in Mammary Stem Cells and Progenitors

Status
Released on 18 November 2014, last updated on 28 November 2014
Organism
Homo sapiens, Mus musculus
Samples (7)
Arrays (2)
Protocols (10)
Description
Triple negative breast cancer (TNBC) has poor prognostic outcome compared to other types of breast cancer1. At present the molecular and cellular mechanisms underlying TNBC pathology are not well understood1. 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. BCL11A overexpression in immortalised human breast epithelial cells promotes tumour formation in xenograft models, whereas knockdown of BCL11A in TNBC cell lines suppresses their tumourigenic potential. In the DMBA-induced mouse mammary tumour model, Bcl11a is found to be essential for tumourigenesis since deletion of Bcl11a before DMBA treatment substantially decreases tumour formation, even in p53-null cells, and inactivation of Bcl11a in established tumours causes their regression. At the cellular level, BCL11A overexpression enhances clonogenicity in vitro whereas its deletion in the mouse causes a reduction in the number of mammary epithelial stem and progenitor cells. Thus, BCL11A has an important role in the genesis of TNBC and in normal mammary epithelial cells. This study highlights the importance of further investigation of BCL11A in breast cancer diagnosis and targeted therapies. [Mouse] KO is bcl11a deleted mammary stem cells. WT are mammary stem cells with intact Bcl11a. [Human] HMLE tumors overexpressing BCL11A.
Experiment type
transcription profiling by array 
Contacts
Jack Chen <geo@ncbi.nlm.nih.gov>, Andy Futreal, Carlos Caldas, Christine J Watson, Fazal Hadi, H R Ali, John Stingl, Juexuan Wang, Mike Stratton, Nancy A Jenkins, Neal G Copeland, Oscar M Rueda, Pentao Liu, Sam Aparicio, Song C Lee, Suet-Feung Chin, Walid T Khaled, Xiongfeng Chen, Yong Yu
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-63386.idf.txt
Sample and data relationshipE-GEOD-63386.sdrf.txt
Processed data (1)E-GEOD-63386.processed.1.zip
Additional data (1)E-GEOD-63386.additional.1.zip
Array designsA-GEOD-10904.adf.txt, A-GEOD-18752.adf.txt
Links