Akt regulates progesterone receptor B-dependent transcription and angiogenesis in endometrial cancer cells.

ABSTRACT: Progestins have long been used clinically for the treatment of endometrial cancers; however, the response rates to progestin therapy vary and the molecular mechanisms behind progestin insensitivity are poorly understood. We hypothesized that in PTEN-mutated endometrial cancers, hyperactive Akt signaling downregulates progesterone receptor B (PRB) transcriptional activity, leading to overall impaired progestin responses. We report that inhibition of Akt with the Akt inhibitor, MK-2206 (MK), in conjunction with progestin (R5020) treatment, is sufficient to upregulate a subset of PRB target genes in Ishikawa cells stably expressing PRB (PRB-Ishikawa). Through gene ontology analysis of Akt-regulated PRB target genes, angiogenesis was found to be the principle process regulated by Akt-PRB. To f

SUBMITTER: Lee II 

PROVIDER: S-EPMC5031502 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature