Inactivation of TRP53, PTEN, RB1 and/or CDH1 in the ovarian surface epithelium induces ovarian cancer transformation and metastasis.

Inactivation of TRP53, PTEN, RB1 and/or CDH1 in the ovarian surface epithelium induces ovarian cancer transformation and metastasis. Biol Reprod. 2020 Jan 13;: Authors: Shi M, Whorton AE, Sekulovski N, Paquet M, MacLean JA, Song Y, Van Dyke T, Hayashi K Abstract Ovarian cancer (OvCa) remains the most common cause of death from gynecological malignancies. Genetically engineered mouse models have been used to study initiation, origin, progression and/or mechanisms of OvCa. Based on the clinical features of OvCa, we examined a quadruple combination of pathway perturbations including PTEN, TRP53, RB1, and/or CDH1. To characterize the cancer-promoting events in the ovarian surface epithelium (OSE), Amhr2cre/+ mice were used to ablate floxed alleles of Pten, Trp53 and Cdh1, which were crossed with TgK19GT121 mice to inactivate RB1 in KRT19 expressing cells. Inactivation of PTEN, TRP53 and RB1 with or without CDH1 developed Type I low-grade OvCa with enlarged serous papillary carcinomas and some high-grade serous carcinomas (HGSC) at older mice. Initiation of epithelial hyperplasia and micropapillary carcinoma started earlier at 1-mo in the triple mutations of Trp53, Pten and Rb1 mice as compared to 2-mo in quadruple mutations of Trp53, Pten, Rb1 and Cdh1 mice, whereas both genotypes eventually developed enlarged proliferating tumors that invaded into the ovary at 3~4-mo. Mice with triple and quadruple mutations developed HGSC and/or metast...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Tags: Biol Reprod Source Type: research