Evidence for autocrine basis of transformation in NIH-3T3 cells transfected with met/HGF receptor gene.
NIH-3T3 cells transformed with met/HGF receptor gene proliferate in the absence of serum and growth factors. Immunocytochemical staining with anti-HGF antibody revealed intense HGF staining in the transfected cells. Additionally, these cells secrete bioactive HGF as evidenced by the ability of the conditioned media to stimulate met/HGF receptor phosphorylation in epithelial cells, and to promote migration of bovine adrenal capillary endothelial cells in a modified Boyden chamber assay. The migration of endothelial cells could be specifically inhibited by anti-HGF antibody but not by an irrelevant antibody. Suramin, a drug known to disrupt ligand-receptor interactions, inhibits the serum and growth-factor free proliferation, and the endogenous phosphorylation of met/HGF receptor in the transformed cells. Taken together, our data suggests an autocrine mode of transformation in NIH-3T3 cells transfected with met/HGF receptor gene.
Kochhar
K S
KS
Division of Oral Pathology, Northwestern University Medical School, Chicago, IL 60611, USA.
Johnson
M E
ME
Volpert
O
O
Iyer
A P
AP
D016475:3T3 Cells / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013498:Suramin / Q000494:pharmacology; D014162:Transfection / Q000235:genetics*
D000906:Antibodies; D017077:Culture Media, Conditioned; D013498:Suramin; D017228:Hepatocyte Growth Factor; D004247:DNA; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases