CHROMOSOMAL LOCALIZATION OF RAT HEPATOCYTE GROWTH-FACTOR (HGF) AND HGF RECEPTOR (MET) AND CHARACTERIZATION OF HGF RECEPTOR CDNA

The Met protooncogene encodes the tyrosine kinase receptor for the hep atocyte growth factor (HGF), a potent mitogen for hepatocytes and othe r epithelial cells produced by mesenchymal cells. Many of the studies on the physiologic and neoplastic growth of the liver, as well as othe r organs, have been performed in the rat. Therefore, chromosomal mappi ng of the rat Hgf gene and the gene of its receptor is of particular v alue. To achieve this: a probe of the coding part of rat HGF cDNA was used to isolate four genomic probes from a lambda phage rat genomic li brary. These probes were used to map the Hgf gene to Chromosome (Chr) 4q12 by the FISH technique. To obtain a probe for the mapping of the H GF receptor/Met gene, we cloned the complete coding region of the rat HGF receptor mRNA. Complementary DNA (cDNA) was synthesized with rever se transcriptase from total RNA for use as a template for the PCR. The two PCR primers were designed based on human and mouse sequences and were located in the flanking regions of the open reading frame of the HGF receptor mRNA. Amplification resulted in a band of an estimated si ze of 4.1 kb, which was cloned and sequenced. The nucleotide sequence showed about 93% and 85% homology compared with mouse and human HGF re ceptor sequences, respectively. A full-length probe of the coding part of the cDNA was used to map the rat HGF receptor/Met gene to Chr 4q21 by the FISH technique. Therefore, the rat Hgf and HGF receptor/Met ge nes are located relatively close to each other, in a way similar to hu mans but not mice.