ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
PGE2 receptor EP2 mediates the antagonistic effect of COX-2 on TGF-beta signaling during mammary tumorigenesis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- Prostanoid EP₂ Receptors Are Up-Regulated in Human Pulmonary Arterial Hypertension: A Key Anti-Proliferative Target for Treprostinil in Smooth Muscle Cells.International journal of molecular sciences · 2018Trial
- Novel EP2 Antagonist Attenuates Microgliosis and Memory Deficits in Pilocarpine-Induced Status Epilepticus Mice.Journal of medicinal chemistry · 2026Article
- Review
- High Expression of COX-2 Associated with the Depth of Invasion on Acral Melanoma by Increasing TGF-β1.Clinical, cosmetic and investigational dermatology · 2021Article
- EP3 Is an Independent Prognostic Marker Only for Unifocal Breast Cancer Cases.International journal of molecular sciences · 2020Article
- CYLD, a mechanosensitive deubiquitinase, regulates TGFβ signaling in load-induced bone formation.Bone · 2020Article
- Activation of the prostaglandin EActa physiologica (Oxford, England) · 2019Article
- Prostaglandin E2 Antagonizes TGF-β Actions During the Differentiation of Monocytes Into Dendritic Cells.Frontiers in immunology · 2018Article
- TGF-β Stimulation of EMT Programs Elicits Non-genomic ER-α Activity and Anti-estrogen Resistance in Breast Cancer Cells.Journal of cancer metastasis and treatment · 2017Article
- Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NFκB pathway.Cancer biology & therapy · 2016Article
- Computational Modeling Predicts Simultaneous Targeting of Fibroblasts and Epithelial Cells Is Necessary for Treatment of Pulmonary Fibrosis.Frontiers in pharmacology · 2016Article
- Prostaglandin E2 and the EP receptors in malignancy: possible therapeutic targets?British journal of pharmacology · 2015Review
- miR-620 promotes tumor radioresistance by targeting 15-hydroxyprostaglandin dehydrogenase (HPGD).Oncotarget · 2015Article
- Identifying Mechanisms of Homeostatic Signaling in Fibroblast Differentiation.Bulletin of mathematical biology · 2015Article
- The role of cytokines in breast cancer development and progression.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2015Review
- Association of EP2 receptor and SLC19A3 in regulating breast cancer metastasis.American journal of cancer research · 2015Article
- TGF-β Suppresses COX-2 Expression by Tristetraprolin-Mediated RNA Destabilization in A549 Human Lung Cancer Cells.Cancer research and treatment · 2015Article
- EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer.Prostate cancer and prostatic diseases · 2014Article
- Prostaglandin receptors EP1-4 as a potential marker for clinical outcome in urothelial bladder cancer.American journal of cancer research · 2014Article
- The relevance of the TGF-β Paradox to EMT-MET programs.Cancer letters · 2013Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The molecular mechanisms that enable cyclooxygenase-2 (COX-2) and its mediator prostaglandin E2 (PGE2) to inhibit transforming growth factor-beta (TGF-beta) signaling during mammary tumorigenesis remain unknown. We show here that TGF-beta selectively stimulated the expression of the PGE2 receptor EP2, which increased normal and malignant mammary epithelial cell (MEC) invasion, anchorage-independent growth, and resistance to TGF-beta-induced cytostasis. Mechanistically, elevated EP2 expression in normal MECs inhibited the coupling of TGF-beta to Smad2/3 activation and plasminogen activator inhibitor-1 (PAI1) expression, while EP2 deficiency in these same MECs augmented Smad2/3 activation and PAI expression stimulated by TGF-beta. Along these lines, engineering malignant MECs to lack EP2 expression prevented their growth in soft agar, restored their cytostatic response to TGF-beta, decreased their invasiveness in response to TGF-beta, and potentiated their activation of Smad2/3 and expression of PAI stimulated by TGF-beta. More important, we show that COX-2 or EP2 deficiency both significantly decreased the growth, angiogenesis, and pulmonary metastasis of mammary tumors produced in mice. Collectively, this investigation establishes EP2 as a potent mediator of the anti-TGF-beta activities elicited by COX-2/PGE2 in normal and malignant MECs. Our findings also suggest that pharmacological targeting of EP2 receptors may provide new inroads to antagonize the oncogenic activities of TGF-beta during mammary tumorigenesis.-Tian, M., Schiemann, W. P. PGE2 receptor EP2 mediates the antagonistic effect of COX-2 on TGF-beta signaling during mammary tumorigenesis.
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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.