Abstract 4200: Transgenic mice overexpressing a Claudin-6 tail deletion mutant are resistant to tumor formation
Notice bibliographique
Résumé
Abstract Morphological and physiological observations suggest that the tight junction (TJ)-based permeability barrier is modified/disrupted during tumorigenesis. It is now also widely recognized that the Claudin (Cldn) family of four tetraspan transmembrane proteins is crucial for tight junction assembly and permeability barrier function. However, the detailed roles of the Cldn cytoplasmic tail and extracellular loop domains in these processes or their dysfunction in tumorigenesis are not yet understood. We recently demonstrated that the tail domain of Cldn6 is crucial for membrane targeting and epidermal permeability barrier (EPB) formation, by forced expression of a Cldn6 tail deletion mutant (CDelta187) via the involucrin (Inv) promoter in the suprabasal compartment of the mouse epidermis. Even though a functional barrier formed, Inv-CDelta187 mice displayed histological and biochemical abnormalities in the epidermal differentiation program leading to a thickening of the epidermis after 1 week of age that persisted throughout life. Notably, a significant amount of not only Cldn6, but also Cldn10, Cldn11, and Cldn18 remained cytoplasmically localized and the protein-unfolding pathway was activated in transgenic epidermal cells. Using a well-established two-stage chemical carcinogenesis model, we are now investigating the temporal and spatial changes in expression of these and other (Cldn1, Cldn12) Cldns that we have previously demonstrated to be important in epidermal differentiation and tumorigenesis in CDelta187 versus wild type (WT) mice. METHODS: The lower dorsal backskin of mice was treated topically with 7,12-dimethylbenz(a)anthracene (DMBA; 0.25 mg/ml in acetone) and following a 10-day incubation period, 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 25 microg/ml in acetone) was applied three times a week to the same area. Backskin samples were dissected 2, 4, 6, 8 and 12 weeks after the initiation of the experimental protocol and immunohistochemistry was performed on sections using antibodies against the following: Cldn1, Cldn6, Cldn11, Cldn12, Cldn18, Ki67 (proliferation marker) and CD3 (immune infiltration marker). Strikingly, epidermal tumor formation was inhibited in CDelta187 as compared to WT animals. This is the first demonstration that alterations in Cldn structure and homeostasis may play a protective role against DMBA/TPA-induced skin tumors. Further investigation into the molecular mechanisms underlying this protective function is underway. Supported by CIHR Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4200.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».