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Neoplasia. 2008 Aug;10(8):847-56.

Altered fibroblast growth factor receptor 4 stability promotes prostate cancer progression.

Author information

1
Department of Pathology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030, USA.

Abstract

Fibroblast growth factor receptor 4 (FGFR-4) is expressed at significant levels in almost all human prostate cancers, and expression of its ligands is ubiquitous. A common polymorphism of FGFR-4 in which arginine (Arg(388)) replaces glycine (Gly(388)) at amino acid 388 is associated with progression in human prostate cancer. We show that the FGFR-4 Arg(388) polymorphism, which is present in most prostate cancer patients, results in increased receptor stability and sustained receptor activation. In patients bearing the FGFR-4 Gly(388) variant, expression of Huntingtin-interacting protein 1 (HIP1), which occurs in more than half of human prostate cancers, also results in FGFR-4 stabilization. This is associated with enhanced proliferation and anchorage-independent growth in vitro. Our findings indicate that increased receptor stability and sustained FGFR-4 signaling occur in most human prostate cancers due to either the presence of a common genetic polymorphism or the expression of a protein that stabilizes FGFR-4. Both of these alterations are associated with clinical progression in patients with prostate cancer. Thus, FGFR-4 signaling and receptor turnover are important potential therapeutic targets in prostate cancer.

PMID:
18670643
PMCID:
PMC2481572
[Indexed for MEDLINE]
Free PMC Article

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