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01-12-2016 | Original Paper

Global or Granulosa Cell-Specific Pten Mutations in Combination with Elevated FSH Levels Fail to Cause Ovarian Tumours in Mice

Authors: Dannielle H. Upton, Kirsty A. Walters, Rachel E. Allavena, Mark Jimenez, Reena Desai, David J. Handelsman, Charles M. Allan

Published in: Discover Oncology | Issue 5-6/2016

Abstract

Phosphatase and tensin homologue (PTEN) is a known tumour suppressor. To explore the role of Pten in ovarian tumorigenesis, we used transgenic (Tg) SOX2. Cre and AMH. Cre mouse models to direct global Pten haploinsufficiency (Pten ^+/−) or ovary-specific granulosa cell (GC) Pten disruption (Pten ^GC). Pten mutant models were combined with progressively rising Tg-follicle-stimulating hormone (TgFSH) levels to study the tumorigenic potential of combined genetic/endocrine modification in vivo. Global Pten ^+/− mice exhibited grossly detectable tumours in multiple organs including uterine and mammary tissue and displayed reduced survival. Despite extra-ovarian tumorigenesis, Pten ^+/− females had no detectable ovarian tumours, although elevated corpus luteum numbers increased ovary size and estrous cycling was altered. Combined TgFSH/Pten ^+/−mice also had no ovarian tumours, but early survival was reduced in the presence of TgFSH. Ovary-specific Pten ^GC ± TgFSH females exhibited no detectable ovarian or uterine tumours, and corpus luteum numbers and estrous cycling remained unchanged. The non-tumorigenic ovarian phenotypes in Pten ^+/− and Pten ^GC ± TgFSH mice support the proposal that multi-hit genetic mutations (including ovarian and extra-ovarian tissue) initiate ovarian tumours. Our findings suggest that elevated FSH may reduce early cancer survival; however, the ovary remains remarkably resistant to Pten-induced tumorigenic changes even in the presence of uterine and reproductive cancers.

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Title: Global or Granulosa Cell-Specific Pten Mutations in Combination with Elevated FSH Levels Fail to Cause Ovarian Tumours in Mice
Authors: Dannielle H. Upton
Kirsty A. Walters
Rachel E. Allavena
Mark Jimenez
Reena Desai
David J. Handelsman
Charles M. Allan
Publication date: 01-12-2016
Publisher: Springer US
Published in: Discover Oncology / Issue 5-6/2016
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI: https://doi.org/10.1007/s12672-016-0272-3

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