E-GEOD-43730 - A Myc transcriptional program that is independent of EMT drives a poor prognosis tumor-propagating phenotype in HER2+ breast cancer
Released on 24 September 2013, last updated on 19 August 2015
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
transcription profiling by array
Daniel Roden <email@example.com>, Adrienne Morey, Akira Nguyen, Alexander Swarbrick, Andrea McFarland, Christina Selinger, Christopher J Ormandy, Daniel L Roden, Iva Nikolic, Jaynish Shah, Jessica Yang, Laura A Baker, Mark Cowley, Matthew J Naylor, Radhika Nair, Sandra A O'Toole, Simon Junakar, Sunil R Lakhani, Sunny Ye, Warren Kaplan, Wee S Teo
c-Myc and Her2 cooperate to drive a stem-like phenotype with poor prognosis in breast cancer. Nair R1, Roden DL, Teo WS, McFarland A, Junankar S, Ye S, Nguyen A, Yang J, Nikolic I, Hui M, Morey A, Shah J, Pfefferle AD, Usary J, Selinger C, Baker LA, Armstrong N, Cowley MJ, Naylor MJ, Ormandy CJ, Lakhani SR, Herschkowitz JI, Perou CM, Kaplan W, O'Toole SA, Swarbrick A.