Luminal breast cancers express estrogen (ER) and progesterone (PR) receptors, and respond to endocrine therapies. However, some ER+PR+ tumors display intrinsic or acquired resistance, possibly related to PR. Two PR isoforms, PR-A and PR-B, regulate distinct gene subsets that may differentially influence tumor fate. A high PR-A:PR-B ratio is associated with poor prognosis and tamoxifen resistanc...

OBJECTIVE Progesterone (P4) plays a central role in women's health. Synthetic progestins are used clinically in hormone replacement therapy (HRT), oral contraceptives, and for the treatment of endometriosis and infertility. Unfortunately, synthetic progestins are associated with side effects, including cardiovascular disease and breast cancer. Botanical dietary supplements are widely consumed f...

Ovulation is a precisely timed process by which a mature oocyte is released from an ovarian follicle. This process is initiated by the pituitary surge of luteinizing hormone (LH), is temporally associated with transcriptional regulation of numerous genes, and is presumed to involve the synthesis and/or activation of specific proteases that degrade the follicle wall. The progesterone receptor (P...

Human progesterone receptor (PR) contains a motif that interacts with the SH3 domain of Src and mediates rapid activation of Src and downstream MAPK (Erk-1/-2) without relying on the transcriptional activity of the receptor. Here we investigated the role and intracellular location of this nontranscriptional activity of PR. Progestin activation of Src/MAPK occurred outside the nucleus with the B...

Despite the pleiotropic effects of the progesterone receptor in breast cancer, the molecular mechanisms in play remain largely unknown. To gain a global view of the PR-orchestrated networks, we used next-generation sequencing to determine the progestin-regulated transcriptome in T47D breast cancer cells. We identify a large number of PR target genes involved in critical cellular programs, such ...

PR-Set7/Set8/KMT5a is a chromatin-modifying enzyme that specifically monomethylates lysine 20 of histone H4 (H4K20me1). In this study we attempted to identify PR-Set7-interacting proteins reasoning that these proteins would provide important insights into the role of PR-Set7 in transcriptional regulation. Using an unbiased yeast two-hybrid approach, we discovered that PR-Set7 interacts with the...

The transcriptional effects of the ovarian hormone progesterone are pleiotropic, and binding to DNA of the nuclear progesterone receptor (PR), a ligand-activated transcription factor, results in diverse outcomes in a range of target tissues. To determine whether distinct patterns of genomic interaction of PR contribute to the cell specificity of the PR transcriptome, we have compared the genomi...

TRANSPARENT TESTA GLABRA (TTG) proteins that contain the WD40 protein interaction domain are implicated in many signalling pathways in plants. The salicylic acid (SA) signalling pathway regulates the resistance of plants to pathogens through defence responses involving pathogenesis-related (PR) gene transcription, activated by the NPR1 (nonexpresser of PR genes 1) protein, which contains WD40-b...

For rat pituitary cells, progesterone receptor (PR) protein localizes to gonadotropes and PR messenger RNA is induced by E2 and rapidly but transiently down-regulated by progesterone. Here we quantitatively establish the down-regulatory effect of progesterone on PR protein and evaluate possible mechanisms. Nuclear PR-immunoreactivity (PR-IR) in gonadotropes, identified by dual immunofluorescenc...

Here, we sought to obtain evidence that the progesterone receptor (PR) may be functional in ovarian cancer and regulated by estrogen. Megestrol acetate inhibited growth of the PR-positive PE04 ovarian carcinoma xenograft but not the PR-negative HOX 60 xenograft. PR concentration was higher in early-stage (I/II) tumors than in advanced-stage (III/IV) tumors (P = 0.007) and in tumors of endometri...