Abstract 4674: Localization of estrogen receptor α(ERα) at the centrosome and its regulation by protein kinases in breast cancer cells
Notice bibliographique
Résumé
Abstract The centrosome plays a key role in the regulation of cell cycle progression. Centrosome amplification or defects are directly linked to aneuploidy and chromosomal instability, which are frequently observed in numerous human cancers. In breast tumors, cancer cells which undergo unrestricted divisions have both structurally and functionally abnormal centrosomes. Estrogen receptor-α (ERα) is known as a nuclear transcriptional factor, which is expressed in two thirds of primary breast cancers. ERα modulates cell proliferation in breast cancer cells by influencing the expression of target genes. Measuring ERα status is of clinical importance in breast cancer diagnostics and determination of treatment response to hormone therapy. Despite extensive studies on its function and mode of regulation on transcription, the exact roles of ERα in cell cycle regulation and centrosome function in breast cancer cells are largely unknown. In this study, we use immunofluorescence assay (IF), biochemical analysis of isolated centrosomes and proximity ligation assay (PLA) to show, for the first time, that ERα is a novel centrosomal protein in the breast tumor cell line MCF7. To search for kinases possibly involved in the regulation of ERα in the centrosome, we focus on three mitotic serine/threonine kinases: Aurora A kinase, Aurora B kinase and Polo-like kinase 1 (PLK1). Aurora A is recruited to centrosomes at G2/M phase and it is required for centrosome maturation and separation, as well as G2/M transition. It was previously shown that Aurora A can phosphorylate ERα at S167 and S305. Aurora B is a chromosome passenger protein which is localized at the midbody and involved in cytokinesis. PLK1 can regulate ERα transcriptional activity during interphase, but it's more widely known functions include driving G2/M transition, and it localizes to centrosomes during metaphase and to the midbody during cytokinesis. By using co-immunoprecipitation (Co-IP) assays, we show that ERα interacts with Aurora A, Aurora B and PLK1 in ER+ MCF7 and T47D cells, and the interactions are increased for Aurora A and PLK1 in the presence of nocodazole which arrested cells at prometaphase. Moreover, PLA showed that ERα interacts with Aurora A mainly in the centrosome region in mitotic MCF7 cells. IF data confirmed that phosphorylated ERα pS118 colocalizes with Aurora A at centrosomes, Aurora B at midzone/midbody, and with PLK1 at centrosome and midbody in mitotic MCF7 and T47D cells. These data suggested that ERα might be directly involved in centrosome function in breast cancer cells, and its dysregulation might play a role in tumor initiation and progression. As a whole, this study reveals a novel and previously unrecognized function for ERα, a finding that could have further implications for finding more accurate biomarkers of prognosis, and providing an alternative treatment strategy against certain types of ER+ breast cancers. Citation Format: Yingfeng Zheng, Christine Bruce, Shihua He, Kirk McManus, Jim Davie, Leigh Murphy. Localization of estrogen receptor α(ERα) at the centrosome and its regulation by protein kinases in breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4674. doi:10.1158/1538-7445.AM2015-4674
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».