Global or granulosa cell-specific Pten mutations in combination with elevated FSH levels fail to cause ovarian tumours in mice

Upton, Dannielle H., Walters, Kirsty A., Allavena, Rachel E., Jimenez, Mark, Desai, Reena, Handelsman, David J. and Allan, Charles M. (2016) Global or granulosa cell-specific Pten mutations in combination with elevated FSH levels fail to cause ovarian tumours in mice. Hormones and Cancer, 7 5-6: 316-326. doi:10.1007/s12672-016-0272-3


Author Upton, Dannielle H.
Walters, Kirsty A.
Allavena, Rachel E.
Jimenez, Mark
Desai, Reena
Handelsman, David J.
Allan, Charles M.
Title Global or granulosa cell-specific Pten mutations in combination with elevated FSH levels fail to cause ovarian tumours in mice
Formatted title
Global or granulosa cell-specific Pten mutations in combination with elevated FSH levels fail to cause ovarian tumours in mice
Journal name Hormones and Cancer   Check publisher's open access policy
ISSN 1868-8500
1868-8497
Publication date 2016-12-01
Year available 2016
Sub-type Article (original research)
DOI 10.1007/s12672-016-0272-3
Open Access Status Not yet assessed
Volume 7
Issue 5-6
Start page 316
End page 326
Total pages 11
Place of publication New York, NY, United States
Publisher Springer New York LLC
Language eng
Formatted 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 (PtenGC). 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 PtenGC ± 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 PtenGC ± 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Veterinary Science Publications
 
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