Decreased expression of keratinocyte growth factor receptor in a subset of human transitional cell bladder carcinomas.

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.

• Authors: S G Diez de Medina, D Chopin, A El Marjou, A Delouvée, W J LaRochelle, A Hoznek, C Abbou, S A Aaronson, J P Thiery, F Radvanyi
• Journal: Oncogene (Oncogene) Vol. 14 Issue 3 Pg. 323-30 (Jan 23 1997) ISSN: 0950-9232 [Print] England
• PMID: 9018118 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neoplasm Proteins
• RNA, Messenger
• Receptors, Fibroblast Growth Factor
• Receptors, Growth Factor
• FGFR2 protein, human
• Receptor Protein-Tyrosine Kinases
• Receptor, Fibroblast Growth Factor, Type 2
• keratinocyte growth factor receptor

Topics

• Adult
• Aged
• Carcinoma, Transitional Cell (metabolism)
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Proteins (metabolism)
• RNA, Messenger (metabolism)
• Receptor Protein-Tyrosine Kinases (metabolism)
• Receptor, Fibroblast Growth Factor, Type 2
• Receptors, Fibroblast Growth Factor (metabolism)
• Receptors, Growth Factor (metabolism)
• Survival Analysis
• Urinary Bladder Neoplasms (metabolism)