ArticleMolecular endocrinology (Baltimore, Md.)2011
p38 and p42/44 MAPKs differentially regulate progesterone receptor A and B isoform stabilization.
Article in Molecular endocrinology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- The hormonal control of parturition.Physiological reviews · 2024Review
- Utilizing an Endogenous Progesterone Receptor Reporter Gene for Drug Screening and Mechanistic Study in Endometrial Cancer.Cancers · 2022Article
- miR-132-3p Modulates DUSP9-Dependent p38/JNK Signaling Pathways to Enhance Inflammation in the Amnion Leading to Labor.International journal of molecular sciences · 2022Article
- Enhancing progestin therapy via HDAC inhibitors in endometrial cancer.American journal of cancer research · 2022Article
- Irilone, a Red Clover Isoflavone, Combined with Progesterone Enhances PR Signaling through the Estrogen and Glucocorticoid Receptors.Journal of natural products · 2021Article
- Triple SILAC identified progestin-independent and dependent PRA and PRB interacting partners in breast cancer.Scientific data · 2021Article
- Sensitivity and Isoform Specificity ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019Article
- Amnion epithelial cell-derived exosomes induce inflammatory changes in uterine cells.American journal of obstetrics and gynecology · 2018Article
- Article
- Sialic Acid-Binding Lectin from Bullfrog Eggs Exhibits an Anti-Tumor Effect Against Breast Cancer Cells Including Triple-Negative Phenotype Cells.Molecules (Basel, Switzerland) · 2018Article
- Inhibiting Nuclear Phospho-Progesterone Receptor Enhances Antitumor Activity of Onapristone in Uterine Cancer.Molecular cancer therapeutics · 2018Article
- Progesterone Receptor Signaling in Uterine Myometrial Physiology and Preterm Birth.Current topics in developmental biology · 2017Review
- Inflammatory Stimuli Increase Progesterone Receptor-A Stability and Transrepressive Activity in Myometrial Cells.Endocrinology · 2017Article
- Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition.Human reproduction update · 2016Review
- Article
- Systematic dissection of the mechanisms underlying progesterone receptor downregulation in endometrial cancer.Oncotarget · 2014Article
- Distribution of estrogen and progesterone receptors isoforms in endometrial cancer.Diagnostic pathology · 2014Article
- Post-translational modifications of the progesterone receptors.The Journal of steroid biochemistry and molecular biology · 2014Review
- A new strategy for selective targeting of progesterone receptor with passive antagonists.Molecular endocrinology (Baltimore, Md.) · 2013Article
- The requirement for p42/p44 MAPK activity in progesterone receptor-mediated gene regulation is target gene-specific.Steroids · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progesterone receptor (PR) isoforms (PRA and PRB) are implicated in the progression of breast cancers frequently associated with imbalanced PRA/PRB expression ratio. Antiprogestins represent potential antitumorigenic agents for such hormone-dependent cancers. To investigate the mechanism(s) controlling PR isoforms degradation/stability in the context of agonist and antagonist ligands, we used endometrial and mammary cancer cells stably expressing PRA and/or PRB. We found that the antiprogestin RU486 inhibited the agonist-induced turnover of PR isoforms through active mechanism(s) involving distinct MAPK-dependent phosphorylations. p42/44 MAPK activity inhibited proteasome-mediated degradation of RU486-bound PRB but not PRA in both cell lines. Ligand-induced PRB turnover required neosynthesis of a mandatory down-regulating partner whose interaction/function is negatively controlled by p42/44 MAPK. Such regulation strongly influenced expression of various endogenous PRB target genes in a selective manner, supporting functional relevance of the mechanism. Interestingly, in contrast to PRB, PRA stability was specifically increased by MAPK kinase kinase 1-induced p38 MAPK activation. Selective inhibition of p42/p44 or p38 activity resulted in opposite variations of the PRA/PRB expression ratio. Moreover, MAPK-dependent PR isoforms stability was independent of PR serine-294 phosphorylation previously proposed as a major sensor of PR down-regulation. In sum, we demonstrate that MAPK-mediated cell signaling differentially controls PRA/PRB expression ratio at posttranslational level through ligand-sensitive processes. Imbalance in PRA/PRB ratio frequently associated with carcinogenesis might be a direct consequence of disorders in MAPK signaling that might switch cellular responses to hormonal stimuli and contribute towards pathogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.