Systematic dissection of the mechanisms underlying progesterone receptor downregulation in endometrial cancer.

ABSTRACT:

Unlabelled

Progesterone, acting through its receptor, PR (progesterone receptor), is the natural inhibitor of uterine endometrial carcinogenesis by inducing differentiation. PR is downregulated in more advanced cases of endometrial cancer, thereby limiting the effectiveness of hormonal therapy. Our objective was to understand and reverse the mechanisms underlying loss of PR expression in order to improve therapeutic outcomes. Using endometrial cancer cell lines and data from The Cancer Genome Atlas, our findings demonstrate that PR expression is downregulated at four distinct levels. In well-differentiated cancers, ligand-induced receptor activation and downregulation are intact. miRNAs mediate fine tuning of PR levels. As differentiation is lost, PR silencing is primarily at the e

SUBMITTER: Yang S 

PROVIDER: S-EPMC4259437 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature