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Wang Y , Cai KQ , Smith ER , Yeasky TM , Moore R , Ganjei-Azar P , Klein-Szanto AJ , Godwin AK , Hamilton TC , Xu XX
Follicle Depletion Provides A Permissive Environment for Ovarian Carcinogenesis
Mol Cell Biol. 2016 Jun 27;36(18) :2418-30
PMID: 27354067 PMCID: PMC5007791 URL: http://www.ncbi.nlm.nih.gov/pubmed/27354067
AbstractWe modeled the etiology of postmenopausal biology on ovarian cancer risk using the germ cell-deficient White-Spotting Variant (Wv) mice, incorporating oncogenic mutations. Ovarian cancer incidence is highest in peri- and post-menopausal women, and epidemiological studies have established the impact of reproductive factors on ovarian cancer risk. Menopause as a result of ovarian follicle depletion is thought to contribute to a higher cancer risk. As a consequence of follicle depletion, the female Wv mice develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis frequently found in post-menopausal human ovaries. Lineage tracing using MISR2-Cre indicated that the tubular adenomas developed in Wv mice were largely derived from MISR2 lineage, which marked only a fraction of ovarian surface and oviduct epithelial cells in wild type tissues. We modeled the etiology of postmenopausal biology on ovarian cancer risk using the germ cell-deficient White-Spotting Variant (Wv) mice, incorporating oncogenic mutations. Deletion of p27, either heterozygous or homozygous, was able to convert the benign tubular adenomas into more proliferative tumors. Restricted deletion of p53 in Wv/Wv mice by either intra-bursal injection of adenoviral Cre or inclusion of MISR2-Cre transgene also resulted in augmented tumor growth. The finding suggests that follicle depletion provides a permissive ovarian environment for oncogenic transformation of epithelial cells, presenting a mechanism for the increased ovarian cancer risk in post-menopausal women.
NotesWang, Ying Cai, Kathy Qi Smith, Elizabeth R Yeasky, Toni M Moore, Robert Ganjei-Azar, Parvin Klein-Szanto, Andres J Godwin, Andrew K Hamilton, Thomas C Xu, Xiang-Xi Mol Cell Biol. 2016 Jun 27. pii: MCB.00202-16.