c-Myc and Her2 cooperate to drive a stem-like phenotype with poor prognosis in breast cancer

Nair, R., Roden, D. L., Teo, W. S., McFarland, A., Junankar, S., Ye, S., Nguyen, A., Yang, J., Nikolic, I., Hui, M., Morey, A., Shah, J., Pfefferle, A. D., Usary, J., Selinger, C., Baker, L. A., Armstrong, N., Cowley, M. J., Naylor, M. J., Ormandy, C. J., Lakhani, S. R., Herschkowitz, J. I., Perou, C. M., Kaplan, W., O'Toole, S. A. and Swarbrick, A. (2013) c-Myc and Her2 cooperate to drive a stem-like phenotype with poor prognosis in breast cancer. Oncogene, 33 30: 3992-4002. doi:10.1038/onc.2013.368

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Author Nair, R.
Roden, D. L.
Teo, W. S.
McFarland, A.
Junankar, S.
Ye, S.
Nguyen, A.
Yang, J.
Nikolic, I.
Hui, M.
Morey, A.
Shah, J.
Pfefferle, A. D.
Usary, J.
Selinger, C.
Baker, L. A.
Armstrong, N.
Cowley, M. J.
Naylor, M. J.
Ormandy, C. J.
Lakhani, S. R.
Herschkowitz, J. I.
Perou, C. M.
Kaplan, W.
O'Toole, S. A.
Swarbrick, A.
Title c-Myc and Her2 cooperate to drive a stem-like phenotype with poor prognosis in breast cancer
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
1476-5594
Publication date 2013-09-23
Year available 2013
Sub-type Article (original research)
DOI 10.1038/onc.2013.368
Open Access Status Not Open Access
Volume 33
Issue 30
Start page 3992
End page 4002
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
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 independent of an epithelial–mesenchymal transition programme or regulation of conventional cancer stem cell markers. Instead, Her2 and c-Myc cooperated to induce the expression of lipoprotein lipase, which was required for proliferation and self-renewal in vitro. HER2 and MYC were frequently coamplified in breast cancer, associated with aggressive clinical behaviour and poor outcome. Lastly, we show that in HER2+ breast cancer patients receiving adjuvant chemotherapy (but not targeted anti-Her2 therapy), MYC amplification is associated with a poor outcome. These findings demonstrate the importance of molecular and cellular context in oncogenic transformation and acquisition of a malignant stem-like phenotype and have diagnostic and therapeutic consequences for the clinical management of HER2+ breast cancer.
Keyword Her2
ERBB2
Myc
Cancer stem cell
Transcriptomics
Oncogene cooperation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Advance online publication 23 September 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 35 times in Scopus Article | Citations
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Created: Wed, 12 Mar 2014, 21:03:38 EST by Roheen Gill on behalf of UQ Centre for Clinical Research