Loss of organic cation transporter 3 (Oct3) leads to enhanced proliferation and hepatocarcinogenesis
| Autor: | Arno Schad, Dirk Gründemann, Johanna Vollmar, Peter R. Galle, Jens U. Marquardt, Tim Zimmermann, Jan Baumgart, Marcus A. Wörns, Anja Lautem, P. M. Fuchs, Daniel Grimm, Ellen I. Closs, Yong Ook Kim, Jörn M. Schattenberg, Detlef Schuppan, Beate K. Straub, N Gehrke |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cyclin D SLC22A3 03 medical and health sciences 0302 clinical medicine medicine University medical OCT3 knockout SLC22A1 Organic cation transport proteins biology Tumor size Kinase business.industry hepatocarcinogenesis organic cation transporter medicine.disease Molecular biology humanities 030104 developmental biology Oncology 030220 oncology & carcinogenesis Hepatocellular carcinoma biology.protein business After treatment Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Johanna Vollmar 1 , Anja Lautem 2 , Ellen Closs 3 , Detlef Schuppan 4 , Yong Ook Kim 4 , Daniel Grimm 1 , Jens U. Marquardt 1 , Peter Fuchs 1 , Beate K. Straub 5 , Arno Schad 5 , Dirk Grundemann 6 , Jorn M. Schattenberg 1 , Nadine Gehrke 1 , Marcus A. Worns 1 , Jan Baumgart 7 , Peter R. Galle 1 and Tim Zimmermann 1 1 Department of Internal Medicine, Gastroenterology and Hepatology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany 2 Department of Hepatobiliary and Transplantation Surgery, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany 3 Department of Pharmacology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany 4 Institute of Translational Immunology, Fibrosis and Metabolism Center, Johannes Gutenberg-University Mainz, Mainz, Germany 5 Institute of Pathology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany 6 Department of Pharmacology, University of Cologne, Mainz, Germany 7 Translational Animal Research Center (TARC), Johannes Gutenberg-University Mainz, Mainz, Germany Correspondence to: Tim Zimmermann, email: tim.zimmermann@unimedizin-mainz.de Keywords: organic cation transporter; OCT3 knockout; hepatocarcinogenesis; SLC22A1; SLC22A3 Received: July 07, 2017 Accepted: December 04, 2017 Published: December 18, 2017 ABSTRACT Background: Organic cation transporters (OCT) are responsible for the uptake of a broad spectrum of endogenous and exogenous substrates. Downregulation of OCT is frequently observed in human hepatocellular carcinoma (HCC) and is associated with a poor outcome. The aim of our current study was to elucidate the impact of OCT3 on hepatocarcinogenesis. Methods: Transcriptional and functional loss of OCT was investigated in primary murine hepatocytes, derived from Oct3-knockout (Oct3 -/- ; FVB.Slc22a3 tm1Dpb ) and wildtype (WT) mice. Liver tumors were induced in Oct3 -/- and WT mice with Diethylnitrosamine and Phenobarbital over 10 months and characterized macroscopically and microscopically. Key survival pathways were investigated by Western Blot analysis. Results: Loss of Oct3 -/- in primary hepatocytes resulted in significantly reduced OCT activity determined by [ 3 H]MPP + uptake in vivo . Furthermore, tumor size and quantity were markedly enhanced in Oct3 -/- mice (p |
| Databáze: | OpenAIRE |
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