Journal article
Amplification of R-spondin1 signaling induces granulosa cell fate defects and cancers in mouse adult ovary
MC De Cian, E Pauper, R Bandiera, VPI Vidal, S Sacco, EP Gregoire, AA Chassot, C Panzolini, D Wilhelm, E Pailhoux, SA Youssef, A De Bruin, K Teerds, A Schedl, I Gillot, MC Chaboissier
Oncogene | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/onc.2016.191
Abstract
R-spondin1 is a secreted regulator of WNT signaling, involved in both embryonic development and homeostasis of adult organs. It can have a dual role, acting either as a mitogen or as a tumor suppressor. During ovarian development, Rspo1 is a key factor required for sex determination and differentiation of the follicular cell progenitors, but is downregulated after birth. In human, increased RSPO1 expression is associated with ovarian carcinomas, but it is not clear whether it is a cause or a consequence of the tumorigenic process. To address the role of Rspo1 expression in adult ovaries, we generated an Rspo1 gain-of-function mouse model. Females were hypofertile and exhibited various ovaria..
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Awarded by Ligue Contre le Cancer
Funding Acknowledgements
We thank Mireille Cutajar-Bossert for her work and management of funding and also Fariba Jianmotamedi, Aurelie Charlet and Beatrice Polo for their punctual help in this work. We are thankful to Walter Birchmeier (Berlin, Germany) for the Axin2<SUP>+/LacZ</SUP> mice and Ken Morohashi (Fukuoka, Japan) for the SF1 antibody. We thank Aitana Perea-Gomez for critical reading of the manuscript. This work was supported by grants from the Fondation ARC pour la Recherche sur le Cancer (PJA 20131200236) and Agence Nationale de la Recherche (ANR-09-GENM-009-03 and ANR-11-LABX-0028-01). EP was supported by a fellowship from INRA and Ligue Nationale contre le Cancer.