Aging accelerates while multiparity delays tumorigenesis in mouse models of high-grade serous carcinoma.

ABSTRACT:

Objectives

The "incessant ovulation" hypothesis links increased risk for tubo-ovarian high-grade serous carcinoma (HGSC) due to more ovulations and reduced risk conferred by pre-menopausal exposures like oral contraceptive use, multiparity, and breastfeeding. However, most women diagnosed with HGSC are postmenopausal, implying age is a major risk factor for HGSC. Our mouse model for HGSC, based on tamoxifen (TAM)-induced somatic inactivation of the Brca1, Trp53, Rb1, and Nf1 (BPRN) tumor suppressor genes in oviductal epithelium, recapitulates key genetic, histopathologic, and biological features of human HGSCs. We aimed to credential the model for future efforts to define biological and risk modification factors in HGSC pathogenesis.

Methods

BPRN mice were treated with TAM t

SUBMITTER: Hou X 

PROVIDER: S-EPMC9533776 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature