Journal article
Pro-apoptotic Bim suppresses breast tumor cell metastasis and is a target gene of SNAI2
D Merino, SA Best, ML Asselin-Labat, F Vaillant, B Pal, RA Dickins, RL Anderson, A Strasser, P Bouillet, GJ Lindeman, JE Visvader
Oncogene | Published : 2015
DOI: 10.1038/onc.2014.313
Abstract
Evasion of cell death is fundamental to the development of cancer and its metastasis. The role of the BCL-2-mediated (intrinsic) apoptotic program in these processes remains poorly understood. Here we have investigated the relevance of the pro-apoptotic protein BIM to breast cancer progression using the MMTV-Polyoma middle-T (PyMT) transgenic model. BIM deficiency in PyMT females did not affect primary tumor growth, but substantially increased the survival of metastatic cells within the lung. These data reveal a role for BIM in the suppression of breast cancer metastasis. Intriguingly, we observed a striking correlation between the expression of BIM and the epithelial to mesenchymal transiti..
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Awarded by National Breast Cancer Foundation
Funding Acknowledgements
We are grateful to K Rogers, L Whitehead, C Nowell for help with imaging, K Birchall, L Reid and G Siciliano for animal husbandry; B Helbert and C Young for mouse genotyping; K Breslin, M Robati and K Liu for technical assistance. We thank D Metcalf and JM Adams for useful discussion and advice, LA O'Reilly for antibodies and D Huang for knockout MEF cell lines. This work was supported by the National Health and Medical Research Council, Australia (NHMRC, 461221 and 1016701); NHMRC IRIISS; the Victorian State Government through Victorian Cancer Agency funding of the Victorian Breast Cancer Research Consortium and Operational Infrastructure Support; the Australian Cancer Research Foundation; and The National Breast Cancer Foundation. DM was supported by a NBCF Early Career Fellowship, RLA by a senior NBCF Fellowship, and SAB by a NHMRC Postgraduate Scholarship #1017256. JEV and GJL were supported by an NHMRC Australia Fellowship and Research Fellowship (637307), respectively.