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: | Fébrissy, Chanaëlle, Adlanmerini, Marine, Pequeux, Christel, Boudou, Frédéric, Buscato, Mélissa, Gargaros, Adrien, Gilardi-Bresson, Silveric, Boriak, Khrystyna, Laurell, Henrik, Fontaine, Coralie, Katzenellenbogen, Benita S, Katzenellenbogen, John A, Guillermet-Guibert, Julie, Arnal, Jean-François, Metivier, Raphaël, Lenfant, Françoise |
| المصدر: | Theranostics, 14 (1), 249 - 264 (2024-01-01) |
| بيانات النشر: | Ivyspring International Publisher |
| سنة النشر: | 2024 |
| المجموعة: | University of Liège: ORBi (Open Repository and Bibliography) |
| مصطلحات موضوعية: | Angiogenesis, Endothelial cells, Estrogen Receptor ERα, Tamoxifen, Tumor growth, Estrogen Receptor alpha, Mice, Animals, Estrogen Receptor alpha/genetics, Estrogen Receptor alpha/metabolism, Endothelial Cells/metabolism, Gene Expression, Endothelium/metabolism, Cell Line, Tumor, Tumor Microenvironment/genetics, Tamoxifen/pharmacology, Neoplasms, Endothelium, Tumor Microenvironment, Medicine (miscellaneous), Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Human health sciences, Oncology, Sciences de la santé humaine, Oncologie |
| الوصف: | peer reviewed ; Rationale: 17β-estradiol (E2) can directly promote the growth of ERα-negative cancer cells through activation of endothelial ERα in the tumor microenvironment, thereby increasing a normalized tumor angiogenesis. ERα acts as a transcription factor through its nuclear transcriptional AF-1 and AF-2 transactivation functions, but membrane ERα plays also an important role in endothelium. The present study aims to decipher the respective roles of these two pathways in ERα-negative tumor growth. Moreover, we delineate the actions of tamoxifen, a Selective Estrogen Receptor Modulator (SERM) in ERα-negative tumors growth and angiogenesis, since we recently demonstrated that tamoxifen impacts vasculature functions through complex modulation of ERα activity. Methods: ERα-negative B16K1 cancer cells were grafted into immunocompetent mice mutated for ERα-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 ERα 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 ERα-negative tumors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1838-7640 |
| العلاقة: | https://www.thno.org/v14p0249.htmTest; urn:issn:1838-7640; https://orbi.uliege.be/handle/2268/311356Test; info:hdl:2268/311356; https://orbi.uliege.be/bitstream/2268/311356/1/Febrissy-Tam%20ER-neg%20tumor%20angio-2024.pdfTest; scopus-id:2-s2.0-85181416079; info:pmid:38164151 |
| DOI: | 10.7150/thno.87306 |
| الإتاحة: | https://doi.org/10.7150/thno.87306Test https://orbi.uliege.be/handle/2268/311356Test https://orbi.uliege.be/bitstream/2268/311356/1/Febrissy-Tam%20ER-neg%20tumor%20angio-2024.pdfTest |
| حقوق: | open access ; http://purl.org/coar/access_right/c_abf2Test ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.359705D5 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 18387640 |
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| DOI: | 10.7150/thno.87306 |