ArticleProceedings of the National Academy of Sciences of the United States of America2015
Activation of protein synthesis in mouse uterine epithelial cells by estradiol-17β is mediated by a PKC-ERK1/2-mTOR signaling pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Metabolic remodeling of endometriosis microenvironment: Energy stress and immune evasion.iScience · 2026Review
- mTORC1 as a metabolic rheostat coordinates hormonal signals and cellular proliferation to sustain endometrial competence.Cellular & molecular biology letters · 2026Article
- Detecting metabolic signatures in endometrial cancer: potential applications of Raman spectroscopy.Future oncology (London, England) · 2025Review
- Effect of Zinc on Blood Biochemical and mTOR Gene Expression in Rats with Polycystic Ovarian.Biological trace element research · 2025Article
- Endometrium-derived organoids from cystic fibrosis patients and mice as new models to study disease-associated endometrial pathobiology.Cellular and molecular life sciences : CMLS · 2025Article
- mTORC1 syndrome (TorS): unifying paradigm for PASC, ME/CFS and PAIS.Journal of translational medicine · 2025Review
- Prospects for potential therapy targeting immune‑associated factors in endometriosis (Review).Molecular medicine reports · 2025Review
- Rapamycin inhibits tamoxifen-induced endometrial proliferation in vitro as a pilot approach for endometrial protection in breast cancer.Scientific reports · 2025Article
- Effect of dietary patterns and nutritional supplementation in the management of endometriosis: a review.Frontiers in nutrition · 2025Review
- Unraveling the Dynamics of Estrogen and Progesterone Signaling in the Endometrium: An Overview.Cells · 2024Review
- Focusing on the role of protein kinase mTOR in endometrial physiology and pathology: insights for therapeutic interventions.Molecular biology reports · 2024Review
- Molecular Mechanisms of Endometriosis Revealed Using Omics Data.Biomedicines · 2023Review
- Transcriptional response of endometrial cells to Insulin, cultured using microfluidics.Reproduction & fertility · 2023Article
- The effect of the menstrual cycle on the circulating microRNA pool in human plasma: a pilot study.Human reproduction (Oxford, England) · 2023Article
- mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation.Cell death & disease · 2022Article
- Activation function 1 of progesterone receptor is required for progesterone antagonism of oestrogen action in the uterus.BMC biology · 2022Article
- The Role of mTOR and eIF Signaling in Benign Endometrial Diseases.International journal of molecular sciences · 2022Review
- The effect of dexamethasone on uterine receptivity, mediated by the ERK1/2-mTOR pathway, and the implantation window: An experimental study.International journal of reproductive biomedicine · 2022Article
- Novel polymer-based system for intrauterine delivery of everolimus for anti-cancer applications.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
- The specific PKC-α inhibitor chelerythrine blunts costunolide-induced eryptosis.Apoptosis : an international journal on programmed cell death · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The uterine epithelium of mice and humans undergoes cyclical waves of cell proliferation and differentiation under the regulation of estradiol-17β (E2) and progesterone (P4). These epithelial cells respond to E2 with increased protein and DNA synthesis, whereas P4 inhibits only the E2-induced DNA synthetic response. Here we show that E2 regulates protein synthesis in these epithelial cells through activating PKC that in turn stimulates ERK1/2 to phosphorylate and thereby activate the central regulator of protein synthesis mechanistic target of rapamycin (mTOR). This mTOR pathway is not inhibited by P4. Inhibitor studies with an estrogen receptor (ESR1) antagonist showed the dependence of this mTOR pathway on ESR1 but that once activated, a phosphorylation cascade independent of ESR1 propagates the pathway. E2 also stimulates an IGF1 receptor (IGF1R) to PI3 kinase to AKT to GSK-3β pathway required for activation of the canonical cell cycle machinery that is inhibited by P4. PKC activation did not stimulate this pathway nor does inhibition of PKC or ERK1/2 affect it. These studies therefore indicate a mechanism whereby DNA and protein synthesis are regulated by two ESR1-activated pathways that run in parallel with only the one responsible for the initiation of DNA synthesis blocked by P4. Inhibition of mTOR by rapamycin in vivo resulted in inhibition of E2-induced protein and DNA synthesis. Proliferative diseases of the endometrium such as endometriosis and cancer are common and E2 dependent. Thus, defining this mTOR pathway suggests that local (intrauterine or peritoneal) rapamycin administration might be a therapeutic option for these diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.