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Deficient expression of mRNA for the putative inductive factor bone morphogenetic protein-7 in chemically initiated
K G Higinbotham1, I D Karavanova, B A Diwan
1Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA.
Abstract:
Wilms' tumor, or nephroblastoma, arises from metanephric blastema and caricatures renal organogenesis. An alteration in at least one of the genes involved in control of renal differentiation is therefore a likely event in tumorigenesis, and indeed some of the genes involved in renal development, for example, hepatocyte growth factor (HGF) and its receptor c-met, the transcription factor Wilms' tumor gene (WT1), and transforming growth factor-beta family member bone morphogenetic protein (BMP)-7, have also been implicated in various models of tumorigenesis. In a comparison of mRNA expression patterns for these genes in normal rat embryonic or fetal kidney and nephroblastoma, we found that the patterns for HGF, met, and WT1 detected by in situ hybridization or ribonuclease protection assay (RPA) in the nephroblastomas were similar to those of normal developing kidney. BMP-7 expression, on the other hand, was lower in most tumors examined both by in situ hybridization and RPA than in normal tissues. This deficiency in a defined inductive factor that has been shown to function in renal tubulogenesis may play a role in tumorigenesis by allowing the accumulation of blastemal populations typical of nephroblastomas.
Insights
Wilms tumor (nephroblastoma) development may be linked to reduced Bone Morphogenetic Protein-7 (BMP-7) levels. This deficiency in BMP-7, crucial for kidney development, might promote tumor growth by allowing abnormal cell accumulation.
Area of Science:
- Developmental Biology
- Cancer Biology
- Molecular Oncology
Background:
- Wilms tumor (nephroblastoma) originates from metanephric blastema, mimicking abnormal renal organogenesis.
- Genes regulating renal differentiation, including HGF, c-met, WT1, and BMP-7, are implicated in kidney development and tumorigenesis.
Purpose of the Study:
- To compare mRNA expression patterns of key renal development genes in normal rat kidneys and Wilms tumors.
- To investigate the potential role of specific gene expression alterations in nephroblastoma development.
Main Methods:
- In situ hybridization and ribonuclease protection assay (RPA) were used to analyze gene expression.
- Comparison of mRNA expression of HGF, c-met, WT1, and BMP-7 in normal embryonic/fetal rat kidney and nephroblastoma samples.
Main Results:
- Expression patterns for HGF, c-met, and WT1 in nephroblastomas were similar to those in normal developing kidneys.
- BMP-7 expression was significantly lower in most examined Wilms tumors compared to normal kidney tissues.
Conclusions:
- Reduced BMP-7 expression in Wilms tumors may contribute to tumorigenesis.
- This deficiency in BMP-7, an inductive factor for renal tubulogenesis, could facilitate the accumulation of blastemal cells characteristic of nephroblastomas.