TY - JOUR
T1 - Identification of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique
AU - Takahashi, Atsushi
AU - Sasaki, Hiroki
AU - Jin Kim, Sun
AU - Kakizoe, Tadao
AU - Miyao, Noriomi
AU - Sugimura, Takashi
AU - Terada, Masaaki
AU - Tsukamoto, Taiji
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Second Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare of Japan; by Grants-in-Aid from the Ministry of Health and Welfare and from the Ministry of Education, Science and Culture of Japan; and by the Bristol-Myers Squibb Foundation.
PY - 1999/4/21
Y1 - 1999/4/21
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Differential hybridization
KW - Receptor tyrosine kinases
KW - Renal cell carcinoma
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U2 - 10.1006/bbrc.1999.0465
DO - 10.1006/bbrc.1999.0465
M3 - Article
C2 - 10208873
AN - SCOPUS:0033590984
SN - 0006-291X
VL - 257
SP - 855
EP - 859
JO - Biochemical and biophysical research communications
JF - Biochemical and biophysical research communications
IS - 3
ER -