Inhibition of CDK2 reduces EZH2 phosphorylation and reactivates ERα expression in high-grade serous ovarian carcinoma.

ABSTRACT: The cyclin-dependent kinase 2 (CDK2) inhibitor dinaciclib, a potential anti-cancer drug, has been tested in clinical trials and reported to suppress tumor initiating cells. Our recent study demonstrated that pharmacological inhibition of CDK2 or enhancer of zeste homolog 2 (EZH2) allows re-expression of ERα and converts triple-negative breast cancers (TNBC) to luminal ERα-positive, rendering TNBC cells targetable by tamoxifen. Like TNBC, EZH2 is also commonly overexpressed in ovarian cancers, and overexpression of cyclin E1 gene (CCNE1) and/or amplification of its associated kinase CDK2 gene is present in ovarian tumor specimens, both of which are associated with primary treatment resistance and poor outcome in high-grade serous ovarian cancer (HGSC). We determined whether inhibition of CD

SUBMITTER: Han Y 

PROVIDER: S-EPMC7191104 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature