Journal article
Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320
A Bronisz, J Godlewski, JA Wallace, AS Merchant, MO Nowicki, H Mathsyaraja, R Srinivasan, AJ Trimboli, CK Martin, F Li, L Yu, SA Fernandez, T Pecot, TJ Rosol, S Cory, M Hallett, M Park, MG Piper, CB Marsh, LD Yee Show all
NATURE CELL BIOLOGY | NATURE PUBLISHING GROUP | Published : 2012
DOI: 10.1038/ncb2396
Abstract
PTEN (Phosphatase and tensin homolog deleted on chromosome 10) expression in stromal fibroblasts suppresses epithelial mammary tumours, but the underlying molecular mechanisms remain unknown. Using proteomic and expression profiling, we show that Pten loss from mammary stromal fibroblasts activates an oncogenic secretome that orchestrates the transcriptional reprogramming of other cell types in the microenvironment. Downregulation of miR-320 and upregulation of one of its direct targets, ETS2 (v-ets erythroblastosis virus E26 oncogene homolog 2) are critical events in Pten-deleted stromal fibroblasts responsible for inducing this oncogenic secretome, which in turn promotes tumour angiogenesi..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Kara Batte for technical assistance with the microRNA platform, Rumeysa Biyik for bioinformatics assistance, Abdel-Rasoul Mahmoud for statistical assistance and the Ohio State University Human Tissue Resource Network and the Ohio State University Comprehensive Cancer Center Microarray, Nucleic Acids, Proteomic Shared Facilities for technical assistance. This work was funded by grants from the National Institutes of Health to M.C.O. (R01 CA053271, P01CA097189) and to G.L. (R01CA85619, R01HD47470, P01CA097189) and from the Komen Breast Cancer Foundation and Evelyn Simmers Charitable Trust to M.C.O.