THE MET PROTOONCOGENE MESENCHYMAL TO EPITHELIAL-CELL CONVERSION

Coexpression of the human Met receptor and its ligand, hepatocyte grow th factor/scatter factor (HGF/SF), in NIH 3T3 fibroblasts causes the c ells to become tumorigenic in nude mice. The resultant tumors display lumen-like morphology, contain carcinoma-like focal areas with interce llular junctions resembling desmosomes, and coexpress epithelial (cyto keratin) and mesenchymal (vimentin) cytoskeletal markers. The tumor ce lls also display enhanced expression of desmosomal and tight-junction proteins. The apparent mesenchymal to epithelial conversion of the tum or cells mimics the conversion that occurs during embryonic kidney dev elopment, suggesting that Met-HGF/SF signaling plays a role in this pr ocess as well as in tumors that express both epithelial and mesenchyma l markers.