Transcriptomics

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A Myc transcriptional program that is independent of EMT drives a poor prognosis tumor-propagating phenotype in HER2+ breast cancer


ABSTRACT: 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. Gene expression analysis of Her2, Myc, and Her2 + Myc over expression on MCF10A cells, with MCF10A vector control comparison

REANALYSED by: E-GEOD-43730

ORGANISM(S): Homo sapiens  

SUBMITTER: Sunny Ye   Radhika Nair  Daniel L Roden  Wee S Teo  Jaynish Shah  Sandra A O'Toole  Laura A Baker  Mark Cowley  Daniel Roden  Sunil R Lakhani  Jessica Yang  Adrienne Morey  Christina Selinger  Iva Nikolic  Andrea McFarland  Akira Nguyen  Christopher J Ormandy  Simon Junakar  Matthew J Naylor  Alexander Swarbrick  Warren Kaplan 

PROVIDER: E-GEOD-43730 | ArrayExpress | 2013-09-24

SECONDARY ACCESSION(S): GSE43730PRJNA187182

REPOSITORIES: GEO, ArrayExpress

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Publications


The HER2 (ERBB2) and MYC genes are commonly amplified 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. Coexpression of both oncoproteins in cultured cells led to the activation of a c-Myc transcriptional signature and acquisition of a self-renewing phenotype independe  ...[more]

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