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| Status |
Public on Sep 24, 2013 |
| Title |
A Myc transcriptional program that is independent of EMT drives a poor prognosis tumor-propagating phenotype in HER2+ breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The HER2 (ERBB2) and MYC genes are commonly amplified genes in breast cancer, yet little is known about their molecular and clinical interaction. Using a novel chimeric mammary transgenic approach and in vitro models, we demonstrate markedly increased self renewal and tumour propagating capability of cells transformed with Her2 and c-Myc. Co-expression of both oncogenes in cultured cells led to a pronounced activation of a c-Myc transcriptional signature and acquisition of a self renewing phenotype independent of an EMT programme or regulation of cancer stem cell markers. We show that HER2 and c-MYC are frequently co-amplified in a clinical breast cancer cohort and that co-amplification is strongly associated with aggressive clinical behaviour and poor outcome. Lastly, we show that in patients receiving adjuvant chemotherapy (but not targeted anti-HER2 therapy), MYC amplification is associated with a poor outcome in HER2+ breast cancer patients. These findings demonstrate the importance of molecular context in oncogenic transformation and acquisition of a malignant stem-like phenotype and have important diagnostic and therapeutic consequences for the clinical management of HER2+ breast cancer.
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| Overall design |
Gene expression analysis of Her2, Myc, and Her2 + Myc over expression on MCF10A cells, with MCF10A vector control comparison
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| Contributor(s) |
Nair R, Roden DL, Teo WS, McFarland A, Junakar S, Ye S, Nguyen A, Yang J, Nikolic I, Morey A, Shah J, Selinger C, Baker LA, Cowley M, Naylor MJ, Ormandy CJ, Lakhani SR, Kaplan W, O'Toole SA, Swarbrick A |
| Citation(s) |
24056965 |
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| Submission date |
Jan 24, 2013 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Daniel Roden |
| E-mail(s) |
d.roden@garvan.org.au
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| Organization name |
Garvan Institute
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| Street address |
384 Victoria Street
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| City |
Sydney |
| State/province |
NSW |
| ZIP/Postal code |
2010 |
| Country |
Australia |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA187182 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE43730_RAW.tar |
44.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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