Decreased expression of keratinocyte growth factor receptor in a subset of human transitional cell bladder carcinomas.
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.
Diez de Medina
S G
SG
UMR 144, CNRS/Institut Curie, Paris, France.
Chopin
D
D
El Marjou
A
A
Delouvée
A
A
LaRochelle
W J
WJ
Hoznek
A
A
Abbou
C
C
Aaronson
S A
SA
Thiery
J P
JP
Radvanyi
F
F
D000328:Adult; D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor