INSULIN-LIKE AND INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR TYROSINE-KINASE ACTIVITIES IN HUMAN RENAL-CARCINOMA

被引:64
作者
KELLERER, M
CORLETA, HVE
MUHLHOFER, A
CAPP, E
MOSTHAF, L
BOCK, S
PETRIDES, PE
HARING, HU
机构
[1] INST DIABET FORSCH MUNCHEN, D-80804 MUNICH, GERMANY
[2] UNIV MUNICH, MED KLIN 2, MOLEK ONKOL LAB, D-81377 MUNICH, GERMANY
[3] GSF FORSCHUNGSZENTRUM UNWELT & GESUNDHEIT GMBH, INST KLIN HAMATOL, D-81377 MUNICH, GERMANY
关键词
D O I
10.1002/ijc.2910620502
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We studied expression and functional characteristics of the insulin- and insulin-like-growth-factor-I(IGF-I) receptors in human renal carcinoma. Ligand-binding properties and tyrosine-kinase activity of both receptors, as well as the expression of the 2 isoforms of the human insulin receptor (HIR-A and -B) were analyzed in renal carcinoma and normal adjacent kidney tissue of 8 adult patients. Partially purified insulin- and IGF-I receptors from normal and renal cell carcinoma tissue possessed identical affinities for their ligands. Renal cell carcinoma, however, contained 3- to 4-fold move specific insulin-binding sites and 2-fold more IGF-I binding sites than adjacent normal kidney tissue. In addition, we determined the relative content of insulin/lGF-I receptor hybrids in both tissues. Renal cell carcinoma and adjacent normal tissue revealed similar amounts of insulin/lGF-I receptor hybrids, i.e., 44 +/- 8.2% of tracer IGF-I binding in normal tissue and 46 +/- 12.0% in renal cell carcinoma. When equal amounts of insulin- and IGF-I receptor protein were studied, we found significantly increased receptor autophosphorylation and elevated substrate phosphorylation in carcinoma tissue. To assess whether the differences in insulin-receptor tyrosine-kinase activity were caused by an altered pattern of insulin receptor isoform expression, we determined mRNA levels for HIR-A and -B. The 2 insulin receptor isoforms were, however, expressed in highly variable ratios in both normal and tumor tissue. Our experiments show that renal carcinoma expresses an elevated amount of insulin- and IGF-I receptor protein with increased specific autophosphorylation and tyrosine-kinase activity each. The increase of insulin-receptor tyrosine-kinase activity in renal carcinoma cannot be explained by an altered expression pattern of insulin receptor isoforms. (C) 1995 Wiley-Liss, Inc.
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页码:501 / 507
页数:7
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