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Expression of the insulin like growth factor-binding protein 3 (IGFBP-3) gene is increased in human renal carcinomas
R L Hintz1, S Bock, A V Thorsson
1Department of Medicine III, University of Munich Medical School Grosshadern, Germany.
Abstract:
After we had established that the IGFBP-3 gene is expressed in normal human kidney we examined renal adenocarcinoma tissue for alterations of the expression of this gene. For this purpose we prepared poly(A)+ RNA from normal kidney tissue and adjacent renal adenocarcinoma of 18 adult patients and compared the levels of IGFBP-3 mRNA by Northern analysis in both samples. The mean content by densitometry was markedly increased in the carcinoma tissues; in 17 of 18 patients the carcinoma contained significantly more IGFBP-3 mRNA than the normal kidney sample. The highest mRNA levels were found in patients with N2 and N3 lymph node extensions. Comparative Southern analysis of paired samples of four of these patients did not reveal amplification of the gene as the cause of these increased mRNA levels. In one patient, however, we identified a restriction fragment length polymorphism (RFLP) present in normal and malignant cellular DNA. This suggests a participation of the IGFBP-3 gene in the development of human renal cell cancer.
Insights
Insulin-like growth factor-binding protein 3 (IGFBP-3) mRNA levels are significantly elevated in most renal cell carcinoma tissues compared to normal kidney. This suggests IGFBP-3 gene involvement in kidney cancer development.
Area of Science:
- Molecular biology
- Oncology
- Genetics
Background:
- The insulin-like growth factor-binding protein 3 (IGFBP-3) gene is expressed in normal human kidney.
- Alterations in gene expression are implicated in cancer development.
Purpose of the Study:
- To investigate alterations in IGFBP-3 gene expression in renal adenocarcinoma.
- To determine if IGFBP-3 gene expression levels correlate with tumor stage.
Main Methods:
- Poly(A)+ RNA extraction from normal kidney and adjacent renal adenocarcinoma tissues of 18 patients.
- Northern blot analysis to compare IGFBP-3 mRNA levels.
- Southern analysis to assess gene amplification.
- Restriction Fragment Length Polymorphism (RFLP) analysis.
Main Results:
- IGFBP-3 mRNA levels were markedly increased in carcinoma tissues of 17 out of 18 patients.
- Highest mRNA levels were observed in patients with advanced lymph node involvement (N2 and N3).
- Gene amplification was not identified as the cause of increased mRNA; RFLP was noted in one patient.
Conclusions:
- The IGFBP-3 gene shows significantly altered expression in renal cell carcinoma.
- Elevated IGFBP-3 mRNA levels may play a role in the pathogenesis of human renal cell cancer.
- Further investigation into the functional role of IGFBP-3 in kidney cancer is warranted.