Identification of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique.
To screen the receptor genes in renal cell carcinoma (RCC) associated with angiogenesis, we performed differential hybridization of the cDNA library of membrane-type protein tyrosine kinases (mPTKs). Three thousand plaques of a mPTKs-enriched cDNA library were screened with mPTKs mixture probes produced from hypervascular RCC tissues and RCC cell lines. Six different cDNA fragments of the PTK genes were isolated, and the sequence analysis showed that these represented cDNAs for TIE1, KDR, FMS, FGFR-4, JAK1 and HCK. Of these genes, the expression of TIE1, KDR, and FGFR-4 was studied in RCC tissue and cell lines by Northern blot analysis. We also investigated the expression of vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and their receptor FLT-1. In all the hypervascular RCC tissues, the amounts of mRNAs for KDR and FLT-1 were increased compared to adjacent normal tissues. The TIE1 and FGFR-4 genes were also overexpressed in most of the hypervascular RCC tissues, while no mRNA of KDR, FLT-1, or TIE1 could be detected in any of the four human RCC cell lines. The amounts of the VEGF and PlGF mRNAs were increased in hypervascular RCC tissues, while VEGF mRNA was detected in the four cell lines but PlGF mRNA was not. FGFR-4 mRNA was expressed in three of the four cell lines. These results suggest that KDR, FLT-1, PlGF and TIE1 mRNAs are present in the mesenchymal cells of RCC, while VEGF and FGFR-4 genes are expressed in RCC cells themselves in vivo.
Takahashi
A
A
Department of Urology, Sapporo Medical University School of Medicine, S-1, W-16, Sapporo, 060-8543, Japan.
Sasaki
H
H
Kim
S J
SJ
Kakizoe
T
T
Miyao
N
N
Sugimura
T
T
Terada
M
M
Tsukamoto
T
T
D015152:Blotting, Northern; D016228:Endothelial Growth Factors / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D016236:Genes, fms / Q000235:genetics; D006801:Humans; D053613:Janus Kinase 1; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000235:genetics; D009389:Neovascularization, Pathologic; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051572:Proto-Oncogene Proteins c-hck; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D042810:Receptor, TIE-1; D011956:Receptors, Cell Surface / Q000235:genetics*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics; D042764:Receptors, TIE; D040262:Receptors, Vascular Endothelial Growth Factor; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D000072483:Placenta Growth Factor; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D042810:Receptor, TIE-1; D042764:Receptors, TIE; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; C496631:HCK protein, human; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D051572:Proto-Oncogene Proteins c-hck