PMID- 19123478 OWN - NLM STAT- MEDLINE DCOM- 20090319 LR - 20160303 IS - 1097-0215 (Electronic) IS - 0020-7136 (Linking) VI - 124 IP - 8 DP - 2009 Apr 15 TI - Hepatocarcinogenesis in mice with a conditional knockout of the hepatocyte growth factor receptor c-Met. PG - 1767-72 LID - 10.1002/ijc.24167 [doi] AB - 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 mICROg/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. FAU - Marx-Stoelting, Philip AU - Marx-Stoelting P AD - Department of Toxicology, Institute of Pharmacology and Toxicology, University of Tubingen, Tubingen, Germany. FAU - Borowiak, Malgorzata AU - Borowiak M FAU - Knorpp, Thomas AU - Knorpp T FAU - Birchmeier, Carmen AU - Birchmeier C FAU - Buchmann, Albrecht AU - Buchmann A FAU - Schwarz, Michael AU - Schwarz M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 3IQ78TTX1A (Diethylnitrosamine) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 3.1.3.9 (Glucose-6-Phosphatase) RN - EC 6.3.1.2 (Glutamate-Ammonia Ligase) RN - YQE403BP4D (Phenobarbital) SB - IM MH - Animals MH - Diethylnitrosamine/pharmacology MH - Glucose-6-Phosphatase/metabolism MH - Glutamate-Ammonia Ligase/metabolism MH - Liver/drug effects/metabolism MH - Liver Neoplasms/chemically induced/*genetics MH - Male MH - Mice MH - Mice, Knockout MH - Organ Size MH - Phenobarbital/toxicity MH - Phenotype MH - Proto-Oncogene Proteins c-met/*metabolism MH - Signal Transduction MH - Time Factors EDAT- 2009/01/07 09:00 MHDA- 2009/03/20 09:00 CRDT- 2009/01/07 09:00 PHST- 2009/01/07 09:00 [entrez] PHST- 2009/01/07 09:00 [pubmed] PHST- 2009/03/20 09:00 [medline] AID - 10.1002/ijc.24167 [doi] PST - ppublish SO - Int J Cancer. 2009 Apr 15;124(8):1767-72. doi: 10.1002/ijc.24167.