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Hepatocarcinogenesis in mice with a conditional knockout of the hepatocyte growth factor receptor c‐Met
Author(s) -
MarxStoelting Philip,
Borowiak Malgorzata,
Knorpp Thomas,
Birchmeier Carmen,
Buchmann Albrecht,
Schwarz Michael
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24167
Subject(s) - knockout mouse , carcinogen , hepatocyte growth factor , hepatocyte , medicine , endocrinology , conditional gene knockout , phenobarbital , receptor , biology , 2 acetylaminofluorene , alkaline phosphatase , ratón , cancer research , biochemistry , enzyme , in vitro , phenotype , microsome , gene
The receptor for the hepatocyte growth factor/scatter factor (HGF/SF), c‐Met, plays a role in tumour 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 μg/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. © 2008 Wiley‐Liss, Inc.