Point mutations and overexpression of Ron induce transformation, tumor formation, and metastasis

摘要: The receptor tyrosine kinase Ron is a member of the family that includes proto-oncogene Met and avian oncogene Sea. interaction with its ligand, known as hepatocyte growth factor-like protein (HGFL) or macrophage stimulating (MSP), induces crucial cellular responses including invasive growth, proliferation, cell scattering, branching morphogenesis. Based on homology functional similarities between it was hypothesized may be important in tumor formation metastasis. To test this hypothesis, wild-type mouse three mutant forms containing mutations similar to those found gene human hereditary papillary renal carcinoma (HPRC), were expressed NIH3T3 cells. A transformed phenotype produced lines expressing either mutated proteins. Further, these displayed oncogenic potential by exhibiting increased proliferation constitutive phosphorylation Ron. These also tested for ability form solid tumors. Cells proteins single amino acid substitutions highly tumorigenic vivo. In model experimental metastasis, two altered formed aggressive tumors lungs. results suggest an when overexpressed activated mutation.