Related Experiment Videos
Decreased expression of keratinocyte growth factor receptor in a subset of human transitional cell bladder carcinomas
S G Diez de Medina1, D Chopin, A El Marjou
1UMR 144, CNRS/Institut Curie, Paris, France.
Abstract:
Growth factors and growth factor receptors are involved in tumor progression. The fibroblast growth factor receptor 2 gene encodes distinct isoforms. The isoforms which bind KGF (keratinocyte growth factor or FGF-7) are called KGF-R or FGFR2b. KGF-R is expressed in different epithelia and is involved in the control of epithelial-mesenchymal interactions. Expression of KGF-R mRNA was examined in normal human bladder and transitional cell carcinoma of the bladder (TCC) by semi-quantitative RT-PCR using TFIID and GAPDH as internal standards. In normal bladder, the KGF-R mRNA was detected in the urothelium but not in the underlying stroma. In TCCs, the level of KGF-R mRNA was generally either normal or low. Eighteen out of 54 TCCs had a KGF-R mRNA level below 30% of that found in normal urothelium. This decrease in KGF-R mRNA was not accompanied by an increase in BEK (FGFR2c) mRNA, the other major splice variant of the fibroblast growth factor receptor 2 gene. Expression of the KGF-R was also monitored by immunohistochemistry using a functional KGF-immunoglobulin chimera. The receptor was uniformly expressed throughout the normal urothelium except for the umbrella cells. Immunoreactivity for KGF-R was found to be negative in tumors with low levels of KGF-R mRNA, while the peritumoral normal urothelium was positive. Among patients with muscle invasive tumors, those exhibiting a low level of KGF-R mRNA had a significantly higher proportion of cancer deaths. Our results suggest that decreased expression of KGF-R can be considered as a marker of tumor progression in muscle invasive TCCs.
Insights
Decreased expression of keratinocyte growth factor receptor (KGF-R) in bladder tumors may indicate progression. Low KGF-R mRNA levels in transitional cell carcinoma (TCC) correlate with poorer outcomes in muscle-invasive cases.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Growth factors and their receptors play a role in tumor progression.
- Fibroblast growth factor receptor 2 (FGFR2) gene has distinct isoforms, including KGF-R (FGFR2b), which binds keratinocyte growth factor (KGF) and is crucial for epithelial-mesenchymal interactions.
- KGF-R is expressed in various epithelia, regulating epithelial-mesenchymal interactions.
Purpose of the Study:
- To investigate the expression of KGF-R mRNA and protein in normal human bladder and transitional cell carcinoma (TCC).
- To determine if KGF-R expression levels correlate with tumor progression and patient outcomes in TCC.
Main Methods:
- Semi-quantitative RT-PCR was used to examine KGF-R mRNA levels in normal bladder and TCC tissues, with TFIID and GAPDH as internal standards.
- Immunohistochemistry was employed to assess KGF-R protein expression using a KGF-immunoglobulin chimera.
- Correlation analysis was performed between KGF-R expression levels and clinical outcomes, particularly in muscle-invasive TCC.
Main Results:
- KGF-R mRNA was detected in the urothelium of normal bladders but not in the stroma.
- In TCCs, KGF-R mRNA levels were generally normal or decreased; 18 out of 54 TCCs showed less than 30% of normal KGF-R mRNA levels.
- Immunohistochemistry revealed KGF-R protein expression in normal urothelium (except umbrella cells) and negative or reduced expression in tumors with low KGF-R mRNA.
- Low KGF-R mRNA levels in muscle-invasive TCC patients were associated with a significantly higher proportion of cancer deaths.
Conclusions:
- Decreased expression of KGF-R mRNA and protein is observed in a subset of transitional cell carcinomas.
- Reduced KGF-R expression may serve as a prognostic marker for tumor progression, especially in muscle-invasive TCC.
- Further investigation into the role of KGF-R in bladder cancer pathogenesis is warranted.