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https://hdl.handle.net/123456789/1845| Τύπος: | Αναρτημένη ανακοίνωση (poster) |
| Τίτλος: | Prognostic significance of estrogen receptor beta in early-stage breast cancer |
| Συγγραφέας: | [EL] Μήτσιου, Δήμητρα[EN] Mitsiou, Dimitra [EL] Μελίγκοβα, Αγγελική[EN] Meligova, Aggeliki [EL] Σιάκουλη, Δήμητρα[EN] Siakouli, Dimitra [EL] Zουμπούλη, Mαρία[EN] Zoumpouli, Maria [EL] Στασινοπούλου, Σωτηρία[EN] Stasinopoulou, Sotiria [EL] Γάνου, Βασιλική[EN] Ganou, Vassiliki [EL] Γκότση Ελένη - Φανή[EN] Gkotsi, Eleni - Fani [EL] Χατζηϊωάννου, Αριστοτέλης[EN] Chatziioannou, Aristotelis [EL] Παπαδόδημα, Όλγα[EN] Papadodima, Olga [EL] Αλέξης, Μιχαήλ[EN] Alexis, Michael |
| Ημερομηνία: | 25/05/2021 |
| Περίληψη: | Breast cancer (BC) is the most common cancer among women worldwide. Depending on the level of expression of estrogen receptor (ERα), progesterone receptor (PR), and HER2 oncogene, BC is classified as ERα-positive (ERα+/PR+/HER2±), HER2-overexpressing (ERα-/PR-/HER2+) or triple-negative (ERα-/PR-/HER2-). Adjuvant endocrine therapy (AET) with antiestrogens or aromatase inhibitors is the treatment of choice for early-stage ERα-positive BC. The optimal clinical outcome depends on rational BC patient classification based on clinicopathological variables and established prognostic markers; however residual risk factors cause treatment outcomes to vary significantly. Early-stage ERα-positive BC is known to recur before as well as after the standard 5-year-AET, thus increasing the challenge of choosing the optimal adjuvant treatment to avoid tumor recurrence. Recently BC research focused on ERβ, the second ER isotype. There are five isoforms of ERβ (ERβ1–5), of which only ERβ1 has estrogen and antiestrogen binding ability. ERβ1 and ERβ2 are the isoforms most frequently expressed in BC. The impact of ERβ isoforms on the prognosis and treatment of ERα-positive BC remains elusive. We have previously shown that while low ERβ1 expression is a marker of early relapse of early-stage ERβ+ BC following AET, high ERβ2 expression is a marker of late relapse. In the present study, we analyzed the role of ERβ1 and ERβ2 in modulating the response of ERα-positive BC cells to antiestrogens. We generated clones of MCF7 cells (a model of early-stage ERα-positive BC) expressing ERβ1 (MCF7-ERβ1) or ERβ2 (MCF7-ERβ2), in addition to the inherently expressed ERα, and showed that expression of ERβ1 and ERβ2 sensitized and desensitized, respectively, MCF7 cells to the anti-proliferative effect of antiestrogens as assessed by cell proliferation assays. Cell cycle analysis revealed that in the presence of estradiol, the S phase fraction of MCF7-ERβ1 and MCF7-ERβ2 cells was much lower and similar, respectively, to the S phase fraction of wild-type MCF7 cells. The antiestrogen tamoxifen completely abolished the S phase fraction of MCF7-ERβ1 but not of wild-type MCF7 and MCF7-ERβ2 cells. A combination of tamoxifen and all-trans retinoic acid abolished the S phase fraction of MCF7-ERβ1 and wild-type MCF7 cells but not of MCF7-ERβ2 cells. In addition, MCF7-ERβ1 cells displayed markedly lower anchorage-independence in the presence of post- as well as pre-menopausal levels of estradiol. Analysis of the global transcriptome profiles of wild-type MCF7, MCF7-ERβ1, and MCF7-ERβ2 cells identified gene signatures associated with ERβ1-mediated sensitivity and ERβ2-mediated resistance of MCF7 cells to tamoxifen. Our data reinforce the prognostic significance of ERβ1 and ERβ2 of sensitivity and resistance, respectively, of early-stage ERα-positive BC to AET. |
| Γλώσσα: | Αγγλικά |
| Σελίδες: | 1 |
| Θεματική κατηγορία: | [EL] Βιοχημεία και Μοριακή βιολογία[EN] Biochemistry and Molecular Biology [EL] Βιολογία κυττάρου[EN] Cell Biology |
| Κάτοχος πνευματικών δικαιωμάτων: | © The Author(s) 2021 |
| Όνομα εκδήλωσης: | Steroid Hormones and Receptors in Health and Disease A Research Conference Co-Organized by FASEB and the International Committee on Rapid Responses to Steroid Hormones (RRSH) |
| Τοποθεσία εκδήλωσης: | Virtual Conference |
| Ημ/νία έναρξης εκδήλωσης: | 25/05/2021 |
| Ημ/νία λήξης εκδήλωσης: | 27/05/2021 |
| Σημειώσεις: | This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Validation – Reinforcement of the Prognostic Significance of Estrogen Receptor beta in Early Breast Cancer” (MIS 5050141). |
| Εμφανίζεται στις συλλογές: | Ερευνητικές ομάδες |
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