title: Overexpression of hepatocyte growth factor receptor in renal carcinoma cells indirectly stimulates tumor growth in vivo.
abstract: We examined the role of increased expression of HGFR kinase in in vivo growth of renal carcinoma. Human renal carcinoma cell line, ACHN cells, was transfected with plasmid encoding wild-type HGFR gene to generate cell lines with increased HGFR protein. ACHN cells with elevated HGFR expression, denoted clones 8 and 10, respectively, showed higher basal kinase activities of HGFR and PI3-kinase than those of empty-vector (mock)-transfected cells. Clone 8 and 10 cells grew similar to mock cells in culture. In mice, tumors of these clones grew more rapidly than those of mock cells. Microvessel density of clone 8 or 10 tumors was higher than that of mock tumors. Clone 8 and 10 cells secreted vascular endothelial growth factor-A (VEGF-A) more than mock cells and the secretion was PI3-kinase inhibitor, LY294002-sensitive. Anti-VEGF-A neutralizing antibody significantly inhibited tumor growth of clones 8 and 10 in mice. These results indicate for the first time that overexpression of HGFR tyrosine kinase in renal carcinoma cells participates in rapid tumor growth in vivo.
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Medical Science, Nagasaki, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Miyata
authors.forename: Shingo
authors.initials: S
authors.lastname: Ashida
authors.forename: Takao
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Koga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanetake
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kanda
mesh_terms: D000818:Animals; D002867:Chromones / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009025:Morpholines / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A
chemical_list: D002867:Chromones; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met; D042461:Vascular Endothelial Growth Factor A; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one