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Verfasst von:Delogu, Salvatore [VerfasserIn]   i
 Longerich, Thomas [VerfasserIn]   i
 Waldburger, Nina [VerfasserIn]   i
 Breuhahn, Kai [VerfasserIn]   i
Titel:SKP2 cooperates with N-Ras or AKT to induce liver tumor development in mice
Verf.angabe:Salvatore Delogu, Chunmei Wang, Antonio Cigliano, Kirsten Utpatel, Marcella Sini, Thomas Longerich, Nina Waldburger, Kai Breuhahn, Lijie Jiang, Silvia Ribback, Frank Dombrowski, Matthias Evert, Xin Chen and Diego F. Calvisi
Jahr:2015
Jahr des Originals:2014
Umfang:13 S.
Fussnoten:Published online December 10, 2014 ; Gesehen am 14.07.2017
Titel Quelle:Enthalten in: OncoTarget
Ort Quelle:[S.l.] : Impact Journals LLC, 2010
Jahr Quelle:2015
Band/Heft Quelle:6(2015), 4, Seite 2222-2234
ISSN Quelle:1949-2553
Abstract:Mounting evidence indicates that S-Phase Kinase-Associated Protein 2 (SKP2) is overexpressed in human hepatocellular carcinoma (HCC). However, the role of SKP2 in hepatocarcinogenesis remains poorly delineated. To elucidate the function(s) of SKP2 in HCC, we stably overexpressed the SKP2 gene in the mouse liver, either alone or in combination with activated forms of N-Ras (N-RasV12), AKT1 (myr-AKT1), or β-catenin (ΔN90-β-catenin) protooncogenes, via hydrodynamic gene delivery. We found that forced overexpression of SKP2, N-RasV12 or ΔN90-β-catenin alone as well as co-expression of SKP2 and ΔN90-β-catenin did not induce liver tumor development. Overexpression of myr-AKT1 alone led to liver tumor development after long latency. In contrast, co-expression of SKP2 with N-RasV12 or myr-AKT1 resulted in early development of multiple hepatocellular tumors in all SKP2/N-RasV12 and SKP2/myr-AKT1 mice. At the molecular level, preneoplastic and neoplastic liver lesions from SKP2/N-RasV12 and SKP2/myr-AKT1 mice exhibited a strong induction of AKT/mTOR and Ras/MAPK pathways. Noticeably, the tumor suppressor proteins whose levels have been shown to be downregulated by SKP2-dependent degradation in various tumor types, including p27, p57, Dusp1, and Rassf1A were not decreased in liver lesions from SKP2/N-RasV12 and SKP2/myr-AKT1 mice. In human HCC specimens, nuclear translocation of SKP2 was associated with activation of the AKT/mTOR and Ras/MAPK pathways, but not with β-catenin mutation or activation. Altogether, the present data indicate that SKP2 cooperates with N-Ras and AKT proto-oncogenes to promote hepatocarcinogenesis in vivo.
DOI:doi:10.18632/oncotarget.2945
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Kostenfrei: Volltext ; Verlag: https://dx.doi.org/10.18632/oncotarget.2945
 Kostenfrei: Volltext: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385847/
 DOI: https://doi.org/10.18632/oncotarget.2945
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:156084714X
Verknüpfungen:→ Zeitschrift

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