Please use this identifier to cite or link to this item: doi:10.22028/D291-28181
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Title: IMP2/IGF2BP2 expression, but not IMP1 and IMP3, predicts poor outcome in patients and high tumor growth rate in xenograft models of gallbladder cancer
Author(s): Kessler, Sonja M.
Lederer, Eva
Laggai, Stephan
Golob-Schwarzl, Nicole
Hosseini, Kevan
Petzold, Johannes
Schweiger, Caroline
Reihs, Robert
Keil, Marlen
Hoffmann, Jens
Mayr, Christian
Kiesslich, Tobias
Pichler, Martin
Kim, Kyung Sik
Rhee, Hyungjin
Park, Young Nyun
Lax, Sigurd
Obrist, Peter
Kiemer, Alexandra
Haybaeck, Johannes
Language: English
Title: Oncotarget
Volume: 8
Issue: 52
Publisher: Impact Journals LLC
Year of Publication: 2017
Publikation type: Journal Article
Abstract: Overexpression of the oncofetal insulin-like growth factor 2 mRNA-binding protein 2 (IMP2/IGF2BP2) has been described in different cancer types. Gallbladder carcinoma (GBC) is a rare but highly aggressive cancer entity with late clinical detection and poor prognosis. The aim of this study was to investigate the role of IMP2 in human GBC. Tissue microarrays (TMAs) of an international multi-center GBC sample collection from n = 483 patients were analyzed by immunohistochemistry. IMP2 immunoreactivity was found in 74.3% of the tumor samples on TMA, of which 14.0% showed strong and 86.0% low staining intensity. 72.4% of the tumor samples were IMP1 positive, but IMP1 showed lower expression in tumor tissue compared to control tissues. IMP3 immunoreactivity was observed in 92.7% of all tumors, of which 53.6% revealed strong IMP3 expression. Kaplan-Meier analysis linked high IMP2 expression to shorter survival time (p = 0.033), whereas neither IMP1 nor IMP3 expression was linked to a decreased survival time. Eight different human biliary tract cancer (BTC) cell lines were evaluated for tumor growth kinetics in mouse xenografts. Cell lines with high IMP2 expression levels showed the fastest increase in tumor volumes in murine xenografts. Furthermore, IMP2 expression in these cells correlated with the generation of reactive oxygen species (ROS) and RAC1 expression in BTC cells, suggesting RAC1-induced ROS generation as a potential mechanism of IMP2-promoted progression of GBC. In conclusion, IMP2 is frequently overexpressed in GBC and significantly associated with poor prognosis and growth rates in vivo. IMP2 might therefore represent a new target for the treatment of advanced GBC.
DOI of the first publication: 10.18632/oncotarget.21116
Link to this record: hdl:20.500.11880/27487
http://dx.doi.org/10.22028/D291-28181
ISSN: 1949-2553
Date of registration: 13-Jul-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Collections:UniBib – Die Universitätsbibliographie

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