TY  - THES
T1  - The IGF2 mRNA binding protein p62 as a regulator of IGF2 and H19 expression - potential implications in tumorigenesis
A1  - Keßler,Sonja
Y1  - 2011/05/26
N2  - Hepatocellular carcinoma (HCC) represents the fifth most common cancer worldwide. The overall survival of patients with HCC is low due to both late diagnosis and the lack of efficient systemic treatment options. Autoantigens are considered as possible diagnostic markers for several types of cancer. Aim of this work was to characterize functional implications of p62/IMP2-2, an insulin-like growth factor 2 (IGF2) mRNA binding protein and autoantigen in HCC, in liver pathogenesis. In transgenic mice expressing p62 only in the liver, levels of both Igf2 mRNA and H19, a non-coding RNA with which it shares an imprinting control region, were strongly elevated. Interestingly, although elevated p62 levels in human HCC tissues correlated with Igf2 expression, the observed antiapoptotic effect of p62 was IGF2-independent, but rather facilitated via extracellular regulated kinase (ERK) activation. p62 attenuated the expression on the tumor suppressor phosphatase and tensin homolog (PTEN), increased the levels of inflammatory cytokines, and altered hepatic fatty acid composition. Taken together, this work provides evidence for p62 being a new interesting target for both diagnostic and therapeutic options in HCC. 
KW  - Insulin-like Growth Factor II
KW  - Autoantigen
KW  - Leberzellkrebs
KW  - Carcinogenese
KW  - HCC
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2011/3975
ER  -