233 ACTIVATION OF ADIPONECTIN RECEPTOR 1 (ADIPOR1) WHICH IS UNDER-EXPRESSED IN KIDNEY CANCER INDUCES TUMOR SUPRESSION
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Résumé
You have accessJournal of UrologyKidney Cancer: Basic Research1 Apr 2011233 ACTIVATION OF ADIPONECTIN RECEPTOR 1 (ADIPOR1) WHICH IS UNDER-EXPRESSED IN KIDNEY CANCER INDUCES TUMOR SUPRESSION Nir Kleinmann, Jian Ping Lu, Laura Beatty, Daniel Gallino, Helga Duivenvoorden, Feng Hou, Richard Austin, Anil Kapoor, and Jehonathan Pinthus Nir KleinmannNir Kleinmann Hamilton, Canada More articles by this author , Jian Ping LuJian Ping Lu Hamilton, Canada More articles by this author , Laura BeattyLaura Beatty Hamilton, Canada More articles by this author , Daniel GallinoDaniel Gallino Hamilton, Canada More articles by this author , Helga DuivenvoordenHelga Duivenvoorden Hamilton, Canada More articles by this author , Feng HouFeng Hou Hamilton, Canada More articles by this author , Richard AustinRichard Austin Hamilton, Canada More articles by this author , Anil KapoorAnil Kapoor Hamilton, Canada More articles by this author , and Jehonathan PinthusJehonathan Pinthus Hamilton, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.302AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Circulating levels of adiponectin, a hormone secreted solely by adipose tissue, have been shown clinically to inversely correlate with metastatic progression of renal cell carcinoma (RCC) but the tumor expression of the adiponectin receptors and their role in adiponectin mediated RCC suppression are currently unknown. METHODS The human CRL-1932 and murine CCL-142 RCC cell lines were used as models. The protein expression levels of the adiponectin receptor AdipoR1 were measured in the tumor and compared to that in the normal parenchyma in 14 patients with clear cell RCC. Secretion of VEGF, MMP2&9 and their inhibitors (TIMP1&2) were measured. MMP2&9 activities and the cell's invasion and migration capacities were measured using enzymatic and basement membrane invasion assays, respectively. These studies were repeated following stable transfection of CRL-1932 cells with 5'-AMP-activated protein kinase alpha specific or control short hairpin RNA (shRNA). The effect of adiponectin on the activation of Akt, AMPK, the mammalian target of rapamycin- mTOR1 and S6K was also examined. CCL-142 cells, stably expressing AdipoR1 specific ShRNA or scrambled ShRNA (control) were injected s.c to C57BL mice and followed for their in-vivo growth. RESULTS Adiponectin inhibited the secretion of VEGF and MMP2&9 while it mediated the increased secretion of TIMP1&2 in a dose-dependent manner. Consequently, the reduced enzymatic activity of MMP2&9 inhibited the cell's invasion and migration potential. These effects were induced by AMPK activation and mTOR inhibition in an Akt independent manner. These tumour suppressive effects were attenuated by AMPKα or AdipoR1 but not AdipoR2 knock down. Likewise, In 11/14 (79%) of the patients examined AdipoR1 expression was reduced compared to the their normal renal tissue. Knock down of AdipoR1 expression accelerated the in-vivo growth of RCC implants. CONCLUSIONS Adiponectin induces its tumor suppression via activation of AMPK through AdipoR1. The entire adiponectin hormonal axis (the hormone-adiponectin and its receptor-AdipoR1) is under activated in RCC. Molecules that can activate AMPK (like metformin) or inhibit mTOR (like Everolimus) may have a role in patients with hypo-adiponectinemia or low tumor expression of AdipoR1 who are at risk for metastatic disease. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e95 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nir Kleinmann Hamilton, Canada More articles by this author Jian Ping Lu Hamilton, Canada More articles by this author Laura Beatty Hamilton, Canada More articles by this author Daniel Gallino Hamilton, Canada More articles by this author Helga Duivenvoorden Hamilton, Canada More articles by this author Feng Hou Hamilton, Canada More articles by this author Richard Austin Hamilton, Canada More articles by this author Anil Kapoor Hamilton, Canada More articles by this author Jehonathan Pinthus Hamilton, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
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 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 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) | 0,027 | 0,005 |
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 ».