Abstract 3347: Post-translational modifications of Akt isoform in chemoresistance of endometrial cancer
Notice bibliographique
Résumé
Abstract Endometrial cancer is ranked fourth in importance among all types of cancer in women. This cancer is the most prevalent gynecological cancer. Akt is an inactive cytosolic serine/threonine kinase that plays a crucial role in cell fate by promoting cellular survival and proliferation. There are three Akt isoforms (1,2 and 3). This protein acts as a key regulator of numerous cellular phenotypes associated with cancer, such as cell proliferation, growth, metabolism, angiogenesis, malignant transformation and chemoresistance. It has been shown that Akt polyubiquitination is increased in cells treated with IGF-1. This ubiquitination is associated with an augmentation in the phosphorylation status of Akt. More and more evidence show that ubiquitination plays a pivotal role in kinase activation. In this study we observed ubiquitinated Akt (Ub-Akt) in the nucleus following IGF-1 treatment in the nucleus of endometrial cell lines (Ishikawa and KLE). We have established the ubiquitination pattern for the three Akt isoforms and their location in the cells. We also showed a cleaved fragment of Akt following cisplatin treatment in the same cell lines. Using western blot analyses, we observed a band at 60kDa corresponding to Akt and also other upper bands corresponding to Ub-Akt, in the nucleus of different endometrial cell lines. We have analyzed the pattern of two endometrial carcinoma (KLE and Ishikawa) and a cervical cancer cell line (HeLa). We found that both Akt1 and Akt3 were ubiquitinated in most of the cell lines. On the other hand, Akt2 was not ubiquitinated in any cell lines. We have used siRNA technology to knockdown each Akt isoform and characterized the loss of each isoform on the ubiquitination pattern for each cell line. We also treated cell lines with cisplatin to see which one of the three isoforms could be involved in chemoresistance and if Akt ubiquitination status could be involved in this process. We have separated fractions of the cytosol from the nucleus for each sample to investigate distribution of Ub-Akt isoforms in each cell line and confirmed the presence of Ub-Akt1 and -3 in the nucleus. We have also co-immunoprecipitated each Akt isoform and Ubiquitin to determine the exact ubiquitination pattern in cancer cells. KLE and Ishikawa had similarities in their pattern. Using immunoprecipitation, we observed that Akt1 was cleaved following cisplatin treatment. We observed that chemosentisitive cells had more cleaved Akt then chemoresistant lines. In conclusion, we are the first to establish a difference in the ubiquitination pattern for the different Akt isoform in the nucleus of endometrial cancer. We are also the first to show a cleavage of Akt isoforms linked to chemosensitive status of endometrial cancer. This study will form the basis for future investigations to determine the role of specific post-translationnal modifications of Akt isoforms in the endometrial cancer. Citation Format: Jérôme Grenier-Naud, Sophie Parent, Eric Asselin. Post-translational modifications of Akt isoform in chemoresistance of endometrial cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3347. doi:10.1158/1538-7445.AM2014-3347
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) | 0,002 | 0,000 |
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 ».