Follicle depletion provides a permissive environment for ovarian carcinogenesis

Ying Wang, Kathy Qi Cai, Elizabeth R. Smith, Toni M. Yeasky, Robert Moore, Parvin Ganjei-Azar, Andres J. Klein-Szanto, Andrew K. Godwin, Thomas C. Hamilton, Xiang Xi Xua

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

We modeled the etiology of postmenopausal biology on ovarian cancer risk using germ cell-deficient white-spotting variant (Wv) mice, incorporating oncogenic mutations. Ovarian cancer incidence is highest in peri- and postmenopausal 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 higher cancer risk. As a consequence of follicle depletion, female Wv mice develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis frequently found in postmenopausal human ovaries. Lineage tracing using MISR2-Cre indicated that the tubular adenomas that developed in Wv mice were largely derived from the MISR2 lineage, which marked only a fraction of ovarian surface and oviduct epithelial cells in wild-type tissues. 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 intrabursal injection of adenoviral Cre or inclusion of the MISR2-Cre transgene also resulted in augmented tumor growth. This 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 postmenopausal women.

Original languageEnglish (US)
Pages (from-to)2418-2430
Number of pages13
JournalMolecular and cellular biology
Volume36
Issue number18
DOIs
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Wang, Y., Cai, K. Q., Smith, E. R., Yeasky, T. M., Moore, R., Ganjei-Azar, P., Klein-Szanto, A. J., Godwin, A. K., Hamilton, T. C., & Xua, X. X. (2016). Follicle depletion provides a permissive environment for ovarian carcinogenesis. Molecular and cellular biology, 36(18), 2418-2430. https://doi.org/10.1128/MCB.00202-16