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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 18, 2014 |
| Title |
BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
[Mouse] KO is bcl11a deleted mammary stem cells. WT are mammary stem cells with intact Bcl11a.
[Human] HMLE tumors overexpressing BCL11A.
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| Contributor(s) |
Khaled WT, Lee SC, Stingl J, Chen X, Ali HR, Rueda OM, Hadi F, Wang J, Yu Y, Chin S, Stratton M, Futreal A, Jenkins NA, Aparicio S, Copeland NG, Watson CJ, Caldas C, Liu P |
| Citation(s) |
25574598 |
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| Submission date |
Nov 18, 2014 |
| Last update date |
Jan 28, 2016 |
| Contact name |
Jack Chen |
| Organization name |
NIH
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| Street address |
SAIC-Frederick Miller Dr
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| City |
Frederick |
| State/province |
MD |
| ZIP/Postal code |
21702 |
| Country |
USA |
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| Platforms (2) |
| GPL10904 |
Illumina HumanHT-12 V4.0 expression beadchip (gene symbol) |
| GPL18752 |
Illumina MouseWG-6 v2.0 expression beadchip [gene symbol version] |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA267658 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE63386_Hs_non-normalized_data.txt.gz |
534.2 Kb |
(ftp)(http) |
TXT |
| GSE63386_Mm_non-normalized_data.txt.gz |
655.5 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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