Hepatocarcinogenesis in mice with a conditional knockout of the hepatocyte growth factor receptor c-Met

被引:22
作者
Marx-Stoelting, Philip [1 ]
Borowiak, Malgorzata [2 ,3 ]
Knorpp, Thomas [4 ]
Birchmeier, Carmen [2 ]
Buchmann, Albrecht [1 ]
Schwarz, Michael [1 ]
机构
[1] Univ Tubingen, Inst Pharmacol & Toxicol, Dept Toxicol, D-72074 Tubingen, Germany
[2] Max Delbruck Zentrum, D-13125 Berlin, Germany
[3] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
[4] NMI, D-75770 Reutlingen, Germany
关键词
tumour initiation; tumour promotion; liver; phenobarbital; c-Met; beta-catenin; MOUSE-LIVER TUMORS; CONSTITUTIVE ACTIVE/ANDROSTANE RECEPTOR; ERK SIGNALING PATHWAY; ENZYME-ALTERED FOCI; BETA-CATENIN; RAT-LIVER; IN-VIVO; B-RAF; PROMOTION; OVEREXPRESSION;
D O I
10.1002/ijc.24167
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The receptor for the hepatocyte growth factor/scatter factor (HGF/SF), c-Met, plays a role in tuinour promotion, progression and metastasis. In this study, we analysed chemically induced hepatocarcinogenesis in mice lacking a functional HGF receptor in their liver. Control and c-Met deficient mice were injected with a single dose of N-nitrosodiethylamine (DEN, 90 mu g/g b.wt.) at 6 weeks of age and mice were subsequently kept on a phenobarbital (PB) containing diet (0.05%) for 35 weeks or on control diet. At the end of the experiment, the carcinogenic response in liver of the animals was monitored. Conditional c-met knockout (KO) mice showed a higher prevalence of macroscopically visible liver tumours and of glutamine synthetase positive and glucose-6-phosphatase deficient lesions in liver. Tumour promotion by PB led to significant increases in the number of preneoplastic and neoplastic lesions in liver of both wild-type and c-met knockout mice, with only minor differences in response. Our results indicate that a defect in c-Met-mediated signaling increases chemically induced tumour initiation in liver but does not significantly affect PB-mediated tumour promotion. (C) Wiley-Liss, Inc.
引用
收藏
页码:1767 / 1772
页数:6
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