ArticleOncotarget2017
Multiple drug resistance-associated protein (MRP4) exports prostaglandin E2 (PGE2) and contributes to metastasis in basal/triple negative breast cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- Tumor Regulatory Effect of 15-Hydroxyprostaglandin Dehydrogenase (HPGD) in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Article
- Structural basis of prostaglandin efflux by MRP4.Nature structural & molecular biology · 2024Article
- Overview of Prostaglandin E2 (PGE2)-Targeting Radiolabelled Imaging Probes from Preclinical Perspective: Lessons Learned and Road Ahead.International journal of molecular sciences · 2023Review
- Targeting Platelet Activation Pathways to Limit Tumour Progression: Current State of Affairs.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Review
- Identification and Characterization of a Novel Dual Inhibitor of Indoleamine 2,3-dioxygenase 1 and Tryptophan 2,3-dioxygenase.International journal of tryptophan research : IJTR · 2022Article
- Progress and challenges of multidrug resistance proteins in diseases.American journal of cancer research · 2022Review
- Drug resistance: from bacteria to cancer.Molecular biomedicine · 2021Review
- Article
- Ganciclovir and Its Hemocompatible More Lipophilic Derivative Can Enhance the Apoptotic Effects of Methotrexate by Inhibiting Breast Cancer Resistance Protein (BCRP).International journal of molecular sciences · 2021Article
- Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities.Current issues in molecular biology · 2021Review
- Novel Symmetrical Cage Compounds as Inhibitors of the Symmetrical MRP4-Efflux Pump for Anticancer Therapy.International journal of molecular sciences · 2021Article
- Pleiotropic Roles of ABC Transporters in Breast Cancer.International journal of molecular sciences · 2021Review
- The Prostaglandin E2 Pathway and Breast Cancer Stem Cells: Evidence of Increased Signaling and Potential Targeting.Frontiers in oncology · 2021Review
- Apigenin by targeting hnRNPA2 sensitizes triple-negative breast cancer spheroids to doxorubicin-induced apoptosis and regulates expression of ABCC4 and ABCG2 drug efflux transporters.Biochemical pharmacology · 2020Article
- Roles of ABCC1 and ABCC4 in Proliferation and Migration of Breast Cancer Cell Lines.International journal of molecular sciences · 2020Article
- Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness.Scientific reports · 2020Article
- The hallmarks of severe pulmonary arterial hypertension: the cancer hypothesis-ten years later.American journal of physiology. Lung cellular and molecular physiology · 2020Review
- Cyp2c44 regulates prostaglandin synthesis, lymphangiogenesis, and metastasis in a mouse model of breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Role of Eicosanoids in Gynecological Malignancies.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Cyclooxygenase-2 (COX-2) and its primary enzymatic product, prostaglandin E2 (PGE2), are associated with a poor prognosis in breast cancer. In order to elucidate the factors contributing to intratumoral PGE2 levels, we evaluated the expression of COX-2/PGE2 pathway members MRP4, the prostaglandin transporter PGT, 15-PGDH (PGE2 metabolism), the prostaglandin E receptor EP4, COX-1, and COX-2 in normal, luminal, and basal breast cancer cell lines. The pattern of protein expression varied by cell line reflecting breast cancer heterogeneity. Overall, basal cell lines expressed higher COX-2, higher MRP4, lower PGT, and lower 15-PGDH than luminal cell lines resulting in higher PGE2 in the extracellular environment. Genetic or pharmacologic suppression of MRP4 expression or activity in basal cell lines led to less extracellular PGE2. The key finding is that xenografts derived from a basal breast cancer cell line with stably suppressed MRP4 expression showed a marked decrease in spontaneous metastasis compared to cells with unaltered MRP4 expression. Growth properties of primary tumors were not altered by MRP4 manipulation. In addition to the well-established role of high COX-2 in promoting metastasis, these data identify an additional mechanism to achieve high PGE2 in the tumor microenvironment; high MRP4, low PGT, and low 15-PGDH. MRP4 should be examined further as a potential therapeutic target in basal breast cancer.
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