دورية أكاديمية
Reprogramming of endothelial gene expression by tamoxifen inhibits angiogenesis and ERα-negative tumor growth
| العنوان: | Reprogramming of endothelial gene expression by tamoxifen inhibits angiogenesis and ERα-negative tumor growth |
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| المؤلفون: | Febrissy, Chanaëlle, Adlanmerini, Marine, Péqueux, Christel, Boudou, Frederic, Buscato, Melissa, Gargaros, Adrien, Gilardi-Bresson, Silveric, Boriak, Khrystyna, Laurell, Henrik, Fontaine, Coralie, Katzenellenbogen, Benita, S., Katzenellenbogen, John, A., Guillermet-Guibert, Julie, Arnal, Jean-François, Metivier, Raphael, Lenfant, Françoise |
| المساهمون: | Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), GIGA Université Liège, Université de Liège, University of Illinois Springfield, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), pour la Recherche Medicale and Region-Occitanie-MP 0014573-FEDER-REGEN-EVE, ANR-18-CE14-0016/ESTROSHEAR, Ligue Nationale contre la Cancer, CNRS, University of Rennes, National Institutes of Health/NCI grant CA220484, BCRF-083, BCRF-084, Breast Cancer Research Foundation, ANR-18-CE14-0016,EstroShear,Rôle du récepteur aux œstrogènes alpha dans la mécanotransduction du flux: conséquences physiopathologiques(2018) |
| المصدر: | ISSN: 1838-7640 ; Theranostics ; https://hal.science/hal-04384793Test ; Theranostics, 2024, Theranostics, 14 (1), pp.249-264. ⟨10.7150/thno.87306⟩. |
| بيانات النشر: | HAL CCSD Ivyspring International Publisher |
| سنة النشر: | 2024 |
| المجموعة: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| مصطلحات موضوعية: | Tamoxifen, Angiogenesis, Estrogen Receptor ER alpha, Endothelial cells, Tumor growth, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Rationale: 17 beta-estradiol (E2) can directly promote the growth of ER alpha-negative cancer cells through activation of endothelial ER alpha in the tumor microenvironment, thereby increasing a normalized tumor angiogenesis. ER alpha acts as a transcription factor through its nuclear transcriptional AF-1 and AF-2 transactivation functions, but membrane ER alpha plays also an important role in endothelium. The present study aims to decipher the respective roles of these two pathways in ER alpha-negative tumor growth. Moreover, we delineate the actions of tamoxifen, a Selective Estrogen Receptor Modulator (SERM) in ER alpha-negative tumors growth and angiogenesis, since we recently demonstrated that tamoxifen impacts vasculature functions through complex modulation of ER alpha activity.Methods: ER alpha-negative B16K1 cancer cells were grafted into immunocompetent mice mutated for ER alpha-subfunctions and tumor growths were analyzed in these different models in response to E2 and/or tamoxifen treatment. Furthermore, RNA sequencings were analyzed in endothelial cells in response to these different treatments and validated by RT-qPCR and western blot.Results: We demonstrate that both nuclear and membrane ER alpha actions are required for the pro-tumoral effects of E2, while tamoxifen totally abrogates the E2-induced in vivo tumor growth, through inhibition of angiogenesis but promotion of vessel normalization. RNA sequencing indicates that tamoxifen inhibits the E2-induced genes, but also initiates a specific transcriptional program that especially regulates angiogenic genes and differentially regulates glycolysis, oxidative phosphorylation and inflammatory responses in endothelial cells.Conclusion: These findings provide evidence that tamoxifen specifically inhibits angiogenesis through a reprogramming of endothelial gene expression via regulation of some transcription factors, that could open new promising strategies to manage cancer therapies affecting the tumor microenvironment of ER ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/38164151; hal-04384793; https://hal.science/hal-04384793Test; https://hal.science/hal-04384793/documentTest; https://hal.science/hal-04384793/file/v14p0249.pdfTest; PUBMED: 38164151 |
| DOI: | 10.7150/thno.87306 |
| الإتاحة: | https://doi.org/10.7150/thno.87306Test https://hal.science/hal-04384793Test https://hal.science/hal-04384793/documentTest https://hal.science/hal-04384793/file/v14p0249.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-ncTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.44723D48 |
| قاعدة البيانات: | BASE |
| DOI: | 10.7150/thno.87306 |
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