Progesterone Receptor-Cyclin D1 Complexes Induce Cell Cycle-Dependent Transcriptional Programs In Breast Cancer Cells

ABSTRACT: Progesterone receptor (PR) and its co-activators are direct targets of activated cyclin dependent kinases (CDKs) in response to peptide growth factors, progesterone, and deregulation of cell cycle inhibitors. Herein, using the T47D breast cancer model, we probed mechanisms of cell cycle-dependent PR action. In the absence of exogenous progestin, PR is specifically phosphorylated during the G2/M phase. Accordingly, numerous PR target genes are cell cycle regulated, including HSPB8, a heat-shock protein whose high expression is associated with tamoxifen-resistance. Progestin-induced HSPB8 expression required cyclin D1 and was insensitive to anti-estrogens, but blocked by anti-progestins or inhibition of specificity factor 1 (SP1). HSPB8 expression increased with or without ligand when cells

ORGANISM(S): Homo sapiens

SUBMITTER: Knutson Todd 

PROVIDER: S-ECPF-GEOD-46715 | biostudies-other |

REPOSITORIES: biostudies-other