Active FOXO1 Is a Key Determinant of Isoform-Specific Progesterone Receptor Transactivation and Senescence Programming.

ABSTRACT:

Unlabelled

Progesterone promotes differentiation coupled to proliferation and prosurvival in the breast, but inhibits estrogen-driven growth in the reproductive tract and ovaries. Herein, it is demonstrated, using progesterone receptor (PR) isoform-specific ovarian cancer model systems, that PR-A and PR-B promote distinct gene expression profiles that differ from PR-driven genes in breast cancer cells. In ovarian cancer models, PR-A primarily regulates genes independently of progestin, while PR-B is the dominant ligand-dependent isoform. Notably, FOXO1 and the PR/FOXO1 target gene p21 (CDKN1A) are repressed by PR-A, but induced by PR-B. In the presence of progestin, PR-B, but not PR-A, robustly induced cellular senescence via FOXO1-dependent induction of p21 and p15 (CDKN2B). Chrom

SUBMITTER: Diep CH 

PROVIDER: S-EPMC4755896 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature