| First Author | Upton DH | Year | 2016 |
| Journal | Horm Cancer | Volume | 7 |
| Issue | 5-6 | Pages | 316-326 |
| PubMed ID | 27506975 | Mgi Jnum | J:320227 |
| Mgi Id | MGI:6869329 | Doi | 10.1007/s12672-016-0272-3 |
| Citation | Upton DH, et al. (2016) Global or Granulosa Cell-Specific Pten Mutations in Combination with Elevated FSH Levels Fail to Cause Ovarian Tumours in Mice. Horm Cancer 7(5-6):316-326 |
| abstractText | 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. |
