Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib.

ABSTRACT: Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy, largely due to metastasis and drug resistant recurrences. Fifteen percent of ovarian tumors carry mutations in BRCA1 or BRCA2, rendering them vulnerable to treatment with PARP inhibitors such as olaparib. Recent studies have shown that TGFβ can induce "BRCAness" in BRCA wild-type cancer cells. Given that TGFβ is a known driver of epithelial to mesenchymal transition (EMT), and the connection between EMT and metastatic spread in EOC and other cancers, we asked if TGFβ and EMT alter the susceptibility of EOC to PARP inhibition. Epithelial EOC cells were transiently treated with soluble TGFβ, and their clonogenic potential, expression, and function of EMT and DNA repair genes, and response to PARP inhibitors compa

SUBMITTER: Roberts CM 

PROVIDER: S-EPMC10417836 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature