RGD Reference Report - The fibroblast growth factor receptor-4 Arg388 allele is associated with prostate cancer initiation and progression. - Rat Genome Database

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The fibroblast growth factor receptor-4 Arg388 allele is associated with prostate cancer initiation and progression.

Authors: Wang, Jianghua  Stockton, David W  Ittmann, Michael 
Citation: Wang J, etal., Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):6169-78. doi: 10.1158/1078-0432.CCR-04-0408.
RGD ID: 150429969
Pubmed: PMID:15448004   (View Abstract at PubMed)
DOI: DOI:10.1158/1078-0432.CCR-04-0408   (Journal Full-text)


PURPOSE: Increased expression of fibroblast growth factors that can activate the fibroblast growth factor receptor-4 (FGFR-4) occurs in a substantial fraction of human prostate cancers in vivo. A germline polymorphism of the FGFR-4 gene resulting in expression of arginine at codon 388 (Arg388) is associated with aggressive disease in patients with breast and colon cancer. We therefore sought to determine whether the FGFR-4 Arg388 allele was associated with prostate cancer incidence and/or the occurrence of aggressive disease.
EXPERIMENTAL DESIGN: The FGFR-4 genotype of men undergoing radical prostatectomy and controls of the same race was determined and the genotype correlated with clinical and pathologic markers of disease aggressiveness. PNT1A cell lines expressing predominantly the FGFR-4 Arg388 or Gly388 allele were established, and cell migration and invasiveness of these cells were assessed by a wounding assay and by quantitative determination of invasion through Matrigel. Expression of urokinase-type plasminogen activator receptor was determined by quantitative RT-PCR and enzyme-linked immunoabsorption assay.
RESULTS: Homozygosity for the FGFR-4 Arg388 allele is strongly associated with the occurrence of prostate cancer in white men. The presence of the FGFR-4 Arg388 allele is also correlated with the occurrence of pelvic lymph node metastasis and biochemical (prostate-specific antigen) recurrence. Expression of FGFR-4 Arg388 in immortalized prostatic epithelial cells results in increased cell motility and invasion through Matrigel and was associated with increased expression of urokinase-type plasminogen activator receptor.
CONCLUSION: The FGFR-4 Arg388 allele is associated with both an increased incidence and clinical aggressiveness of prostate cancer and results in changes in cellular motility and invasiveness in immortalized prostate epithelial cells consistent with the promotion of metastasis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate cancer disease_progressionIAGP 150429969DNA:SNP:exon 9: 288G>A and p.G388R (human)RGD 
prostate cancer disease_progressionISOFGFR4 (Homo sapiens)150429969; 150429969DNA:SNP:exon 9: 288G>A and p.G288R (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Prostate neoplasm disease_progressionIAGP 150429969DNA:SNP:exon 9: 388G>A and p.G288R (human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Fgfr4  (fibroblast growth factor receptor 4)

Genes (Mus musculus)
Fgfr4  (fibroblast growth factor receptor 4)

Genes (Homo sapiens)
FGFR4  (fibroblast growth factor receptor 4)


Additional Information