Transcriptomics

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


ABSTRACT: 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.

ORGANISM(S): Musculus  

SUBMITTER: Suet-Feung Chin   Andy Futreal  Oscar M Rueda  Carlos Caldas  Fazal Hadi  Juexuan Wang  Jack Chen  Neal G Copeland  Christine J Watson  Sam Aparicio  H R Ali  Mike Stratton  Walid T Khaled  Pentao Liu  Yong Yu  Song C Lee  Nancy A Jenkins  Xiongfeng Chen  John Stingl 

PROVIDER: E-GEOD-63386 | ArrayExpress | 2014-11-18

SECONDARY ACCESSION(S): GSE63386PRJNA267658

REPOSITORIES: GEO, ArrayExpress

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