PMID- 10359528
OWN - NLM
STAT- MEDLINE
DCOM- 19990701
LR  - 20091119
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 21
DP  - 1999 May 27
TI  - Amplification and overexpression of the hepatocyte growth factor receptor 
      (HGFR/MET) in rat DMBA sarcomas.
PG  - 3226-34
AB  - In the present study subcutaneous fibrosarcomas were induced by the carcinogen 
      7,12-dimethylbenz(a)anthracene (DMBA) in rats from F1 generation cross breedings 
      of two different inbred strains. Comparative genomic hybridization (CGH) 
      analysis, which allows detection of DNA sequence copy changes, was applied to one 
      of the tumors and it was found that there were increased copy numbers of 
      sequences at chromosome 4q12-q21 in this tumor. We have previously determined 
      that the loci for the hepatocyte growth factor (Hgf) and hepatocyte growth factor 
      receptor (Hgfr/Met), a protooncogene, are situated in this particular chromosome 
      region. Using probes for the two genes in FISH (fluorescence in situ 
      hybridization) and in Southern blots we found that the Hgfr/Met gene was 
      amplified in five of the 19 sarcomas studied, and that the Hgf gene was 
      coamplified in two of them. Northern and Western blots and tyrosine 
      phosphorylation analysis showed that the HGF receptor was overexpressed and 
      functional in all five tumors, as well as in two additional tumors. In summary, 
      both amplification and overexpression of the Hgfr/Met gene was found in about 25% 
      of DMBA-induced experimental rat sarcomas, and HGF receptor overexpression alone 
      was seen in two additional tumors. Possibly this reflects an involvement in 
      paracrine or autocrine stimulation of growth and invasiveness by HGF. Our finding 
      could provide a rodent model system to increased knowledge about causality and 
      therapy, which may be applicable to the sizeable fraction of human 
      musculoskeletal tumors displaying MET overexpression.
FAU - Helou, K
AU  - Helou K
AD  - Department of Cell and Molecular Biology-Genetics, Goteborg University, 
      Gothenburg, Sweden.
FAU - Wallenius, V
AU  - Wallenius V
FAU - Qiu, Y
AU  - Qiu Y
FAU - Ohman, F
AU  - Ohman F
FAU - Stahl, F
AU  - Stahl F
FAU - Klinga-Levan, K
AU  - Klinga-Levan K
FAU - Kindblom, L G
AU  - Kindblom LG
FAU - Mandahl, N
AU  - Mandahl N
FAU - Jansson, J O
AU  - Jansson JO
FAU - Levan, G
AU  - Levan G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Carcinogens)
RN  - 57-97-6 (9,10-Dimethyl-1,2-benzanthracene)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - 9,10-Dimethyl-1,2-benzanthracene/pharmacology
MH  - Animals
MH  - Carcinogens/pharmacology
MH  - Chromosome Mapping
MH  - Disease Models, Animal
MH  - Female
MH  - Fibrosarcoma/chemically induced/*genetics
MH  - Gene Amplification
MH  - Gene Expression
MH  - Hepatocyte Growth Factor/biosynthesis/genetics
MH  - Humans
MH  - Male
MH  - Nucleic Acid Hybridization
MH  - Proto-Oncogene Proteins c-met/*genetics
MH  - Rats
MH  - Rats, Inbred BN
MH  - Rats, Inbred Lew
MH  - Tumor Cells, Cultured
EDAT- 1999/06/08 00:00
MHDA- 1999/06/08 00:01
CRDT- 1999/06/08 00:00
PHST- 1999/06/08 00:00 [pubmed]
PHST- 1999/06/08 00:01 [medline]
PHST- 1999/06/08 00:00 [entrez]
AID - 10.1038/sj.onc.1202658 [doi]
PST - ppublish
SO  - Oncogene. 1999 May 27;18(21):3226-34. doi: 10.1038/sj.onc.1202658.