Journal article

Reactivation of multipotency by oncogenic PIK3CA induces breast tumour heterogeneity

Alexandra Van Keymeulen, May Yin Lee, Marielle Ousset, Sylvain Brohee, Sandrine Rorive, Rajshekhar R Giraddi, Aline Wuidart, Gaelle Bouvencourt, Christine Dubois, Isabelle Salmon, Christos Sotiriou, Wayne A Phillips, Cedric Blanpain

NATURE | NATURE PUBLISHING GROUP | Published : 2015

Abstract

Breast cancer is the most frequent cancer in women and consists of heterogeneous types of tumours that are classified into different histological and molecular subtypes. PIK3CA and P53 (also known as TP53) are the two most frequently mutated genes and are associated with different types of human breast cancers. The cellular origin and the mechanisms leading to PIK3CA-induced tumour heterogeneity remain unknown. Here we used a genetic approach in mice to define the cellular origin of Pik3ca-derived tumours and the impact of mutations in this gene on tumour heterogeneity. Surprisingly, oncogenic Pik3ca(H1047R) mutant expression at physiological levels in basal cells using keratin (K)5-CreER(T2..

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Grants

Funding Acknowledgements

C.B. is an investigator of WELBIO, A.V.K. is Chercheur Qualifie of the FNRS, C.S. is Maitre de Recherche of the FNRS, M.Y.L. is supported by the Agency for Science, Technology and Research (A*STAR, Singapore) fellowship, M.O. and A.W. are supported by FNRS fellowships, R.R.G. is supported by a TELEVIE fellowship and S.B. is supported by the foundation "Amis de l'institut Jules Bordet". The Center for Microscopy and Molecular Imaging is supported by the European Regional Development Fund and Wallonia. W.A.P. is supported by project grants from the National Health and Medical Research Council of Australia. This work was supported by the FNRS, TELEVIE, a research grant from the Fondation Contre le Cancer, the ULB fondation, the Fond Yvonne Boel, the Fond Gaston Ithier, the foundation Bettencourt Schueller, the foundation Baillet Latour, and the European Research Council.