« Back Urologic Oncology: Seminars and Original Investigations

Article in Press

Oncogenic role of fibroblast growth factor receptor 3 in tumorigenesis of urinary bladder cancer

Received 18 May 2010 ,Revised 19 July 2010 ,Accepted 20 July 2010. Published online 07 September 2010 Corrected Proof

References 

  1. Ploeg M, Aben KKH, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol. 2009;27:289–293
  2. American Cancer Society. Cancer Facts and Figures 2009. Atlanta: American Cancer Society; 2009;
  3. Ferlay J, Randi G, Bosetti C, et al. Declining mortality from bladder cancer in Europe. Br J Urol. 2007;101:11–19
  4. Pelucchi C, Bosetti C, Negri E, et al. Mechanisms of disease: The epidemiology of bladder cancer. Nat Clin Pract Urol. 2006;3:327–340
  5. Ferlay J, Bray V, Isani P, et al. GLOBOCAN 2002: Cancer incidence, mortality, and prevalence worldwide. IARC Cancer Base 2004; No. 5. ver. 2.0. IARC Press: Lyon.
  6. Kamarana NM, Kamat MR, Kurkure AP. National Cancer registry project ICMR 2000. Published in 2003.
  7. Dhar GM, Shah GN, Naheed B, et al. Epidemiologic trend in the distribution of cancer in Kashmir Valley. J Epidemiol Community Health. 1993;47:290–292
  8. Jemal A, Siegel R, Ward E. Cancer Statistics, 2007. CA Cancer J Clin. 2007;57:43–66
  9. Riley GF, Potosky AL, Lubitz JD, et al. Medicare payments from diagnosis to death for elderly cancer patients by stage at diagnosis. Med Care. 1995;33:828–841
  10. Crawford JM. The origins of bladder cancer. Lab Investig. 2008;88:686–693
  11. Heney NM. Natural history of superficial bladder cancer (Prognostic features and long term disease course). Urol Clin North Am. 1992;19:429–433
  12. Zeegers MP, Kellen E, Buntinx F, et al. The association between smoking, beverage consumption, diet, and bladder cancer: A systematic literature review. World J Urol. 2004;21:392–401
  13. Clayson DB. Specific aromatic amines as occupational bladder carcinogens. Natl Cancer Inst Monogr. 1981;58:15–19
  14. Droller MJ. Alterations of the p53 gene in occupational bladder cancer in workers exposed to aromatic amines. J Urol. 1998;160:618–623
  15. Wu XR. Urothelial tumorigenesis: A tale of divergent pathways. Nat Rev Cancer. 2005;5:713–725
  16. Knowles MA. Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese?. Carcinogenesis. 2006;27:361–373
  17. Holmang S, Hedelin H, Anderstrom C, et al. The relationship among multiple recurrences, progression, and prognosis of patients with stages Ta and T1 transitional cell cancer of the bladder followed for at least 20 years. J Urol. 1995;153:1823–1826, Discussion 1826–7.
  18. Kurth KH, Denis L, Bouffioux C, et al. Factors affecting recurrence and progression in superficial bladder tumors. Eur J Cancer. 1995;31A:1840–1846
  19. Billerey C, Chopin D, Aubriot-Lorton MH, et al. Frequent FGFR3 mutations in papillary noninvasive bladder (pTa) tumors. Am J Pathol. 2001;158:1955–1959
  20. Cappellen D, De Oliveira C, Ricol D, et al. Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet. 1999;23:18–20
  21. Sibley K, Cuthbert-Heavens D, Knowles MA. Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma. Oncogene. 2001;20:686–691
  22. Kimura T, Suzuki H, Ohashi T, et al. The incidence of thanatophoric dysplasia mutations in FGFR3 gene is higher in low-grade or superficial bladder carcinomas. Cancer. 2001;92:2555–2561
  23. van Rhijn BW, Lurkin I, Radvanyi F, et al. The fibroblast growth factor receptor 3 (FGFR3) mutations is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer Res. 2001;61:1265–1268
  24. Johnson DE, Williams LT. Structural and functional diversity in the FGF receptor multigene family. Adv Cancer Res. 1993;60:1–41
  25. Avivi A, Yayon A, Givol D. A novel form of FGF receptor- 3 using an alternative exon in the immunoglobulin domain III. FEBS Lett. 1993;330:249–252
  26. Ornitz DM, Xu J, Colvin JS, et al. Receptor specificity of the fibroblast growth factor family. J Biol Chem. 1996;271:15292–15297
  27. Werner S, Duan DS, de Vries C, et al. Differential splicing in the extracellular region of fibroblast growth factor receptor 1 generates receptor variants with different ligand-binding specificities. Mol Cell Biol. 1992;12:82–88
  28. Botteman MF, Pashos CL, Redaelli A, et al. The health economics of bladder cancer: A comprehensive review of the published literature. Pharmacoeconomics. 2003;21:1315–1330
  29. Thompson LM, Plummer S, Schalling M, et al. A gene encoding a fibroblast growth factor receptor isolated from the Huntington disease gene region of human chromosome 4. Genomics. 1991;11:1133–1142
  30. Perez-Castro AV, Wilson J, Altherr MR. Genomic organization of the human fibroblast growth factor receptor 3 (FGFR3) gene and comparative sequence analysis with the mouse Fgfr3 gene. Genomics. 1997;41:10–16
  31. Keegan K, Johnson DE, Williams LT, et al. Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3. Proc Natl Acad Sci U S A. 1991;88:1095–1099
  32. Wuchner C, Hilbert K, Zabel B, et al. Human fibroblast growth factor receptor 3 gene (FGFR3): Genomic sequence and primer set information for gene analysis. Hum Genet. 1997;100:215–219
  33. Johnson DE, Williams LT. Structural and functional diversity in the FGF receptor multigene family. Adv Cancer Res. 1993;60:1–41
  34. Delezoide AL, Benoist-Lasselin C, Legeai-Mallet L, et al. Spatio-temporal expression of FGFR 1, 2, and 3 genes during human embryo fetal ossification. Mech Dev. 1998;77:19–30
  35. Murgue B, Tsunekawa S, Rosenberg I, et al. Identification of a novel variant form of fibroblast growth factor receptor 3 (FGFR3 IIIb) in human colonic epithelium. Cancer Res. 1994;54:5206–5211
  36. Chellaiah AT, McEwen DG, Werner S, et al. Fibroblast growth factor receptor (FGFR) 3 (Alternative splicing in immunoglobulin-like domain III creates a receptor highly specific for acidic FGF/FGF-1). J Biol Chem. 1994;269:11620–11627
  37. Passos-Bueno MR, Wilcox WR, Jabs EW, et al. Clinical spectrum of fibroblast growth factor receptor mutations. Hum Mutat. 1999;14:115–125
  38. Webster MK, Donoghue DJ. FGFR activation in skeletal disorders: Too much of a good thing. Trends Genet 11997;3:178–82.
  39. Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev. 2002;16:1446–1465
  40. Bellus GA, Spector EB, Speiser PW, et al. Distinct missense mutations of the FGFR3 Lys 650 codon modulates receptor kinase activation and the severity of the skeletal dysplasia phenotype. Am J Hum Genet. 2000;67:1411–1421
  41. Naski MC, Wang Q, Xu J, et al. Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia. Nat Genet. 1996;13:233–237
  42. Chesi M, Nardini E, Brents LA, et al. Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nat Genet. 1997;16:260–264
  43. Richelda R, Ronchetti D, Baldini L, et al. A novel chromosomal translocation t(4;14)(p16.3;q32) in multiple myeloma involves the fibroblast growth-factor receptor 3 gene. Blood. 1997;90:4062–4070
  44. Jebar AH, Hurst CD, Tomlinson DC, et al. FGFR3 and Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma. Oncogene. 2005;24:5218–5225
  45. Bellus GA, Hefferon TW, Ortiz de Luna RI, et al. Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am J Hum Genet. 1995;56:368–373
  46. van Rhijn BW, van Tilborg AA, Lurkin I, et al. Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders. Eur J Hum Genet. 2002;10:819–824
  47. Birrer MJ, Johnson ME, Sameul CM, et al. Whole genome oligonucleotide based array comparative genomic hybridization analysis identified fibroblast growth factor 1 as a prognostic marker for advanced-stage serous ovarian adenocarcinomas. J Clin Oncol. 2007;25:2281–2287
  48. Marshall CJ. Specificity of receptor tyrosine kinase signaling: Transient vs. sustained extracellular signal-regulated kinase activation. Cell. 1995;80:179–185
  49. Hernandez S, Lopez-Knowles E, Lloreta J, et al. FGFR3 and Tp53 mutations in T1G3 transitional bladder carcinomas: Independent distribution and lack of association with prognosis. Clin Cancer Res. 2005;11:5444–5450
  50. Zieger K, Dyrskjot L, Wiuf C, et al. Role of activating fibroblast growth factor receptor 3 mutations in the development of bladder tumors. Clin Cancer Res. 2005;11:7709–7719
  51. Shiang R, Thompson LM, Zhu YZ, et al. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell. 1994;78:335–342
  52. Lopez-Knowles E, Hernandez S, Malats N, et al. PIK3CA mutations are an early genetic alteration associated with FGFR3 mutations in superficial papillary bladder tumors. Cancer Res. 2006;66:7401–7404
  53. Hernandez S, Lopez-Knowles E, Lloreta J, et al. Prospective study of FGFR3 mutations as a prognostic factor in non-muscle-invasive urothelial bladder carcinomas. J Clin Oncol. 2006;24:3664–3671
  54. Cosgrove DJ, Monga M. Inverted papilloma as a cause of high-grade ureteral obstruction. Urology. 2000;56:856
  55. Amin MB, Gomez JA, Young RH. Urothelial transitional cell carcinoma with endophytic growth patterns: A discussion of patterns of invasion and problems associated with assessment of invasion in 18 cases. Am J Surg Pathol. 1997;21:1057–1068
  56. Eiber M, van Oers JM, Zwarthoff EC, et al. Low frequency of molecular changes and tumor recurrence in inverted papillomas of the urinary tract. Am J Surg Pathol. 2007;31:938–946
  57. Matsumoto M, Ohtsuki Y, Ochii K, et al. Fibroblast growth factor receptor 3 protein expression in urothelial carcinoma of the urinary bladder, exhibiting no association with low-grade and/or noninvasive lesions. Oncol Rep. 2004;12:967–971
  58. Gomez-Roman JJ, Saenz P, Molina M, et al. Fibroblast growth factor receptor 3 is over expressed in urinary tract carcinomas and modulates the neoplastic cell growth. Clin Cancer Res. 2005;11:459–465
  59. Tomlinson D, Baldo O, Knowles MA. FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer. J Pathol. 2007;213:91–98
  60. Lindgren D, Liedberg F, Andersson A, et al. Molecular characterization of early stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q. Oncogene 2006;25:2685–96.
  61. Choi D-Y, Toledo-Aral J-J, Lin HY, et al. Fibroblast growth factor receptor 3 induces gene expression primarily through Ras-independent signal transduction pathways. J Biol Chem. 2001;276:5116–5122
  62. Bakkar AA, Wallerand H, Radvanyi F, et al. FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell carcinoma of the bladder. Cancer Res. 2003;63:8108–8112
  63. Sangar VK, Ragavan N, Matanhelia SS, et al. The economic consequences of prostate and bladder cancer in the UK. BJU Int. 2005;95:59–63
  64. Rieger-Christ K, Mourtzinos A, Lee P, et al. Identification of fibroblast growth factor receptor 3 mutations in urine sediment DNA samples complements cytology in bladder tumor detection. Cancer. 2003;98:737–744
  65. Steiner G, Schoenberg MP, Linn JF, et al. Detection of bladder cancer recurrence by microsatellite analysis of urine. Nat Med. 1997;3:621–624
  66. Hoque MO, Lee J, Begum S, et al. High-throughput molecular analysis of urine sediment for the detection of bladder cancer by high-density single-nucleotide polymorphism array. Cancer Res. 2003;63:5723–5726
  67. Schneider A, Borgnat S, Lang H, et al. Evaluation of microsatellite analysis in urine sediment for diagnosis of bladder cancer. Cancer Res. 2000;60:4617–4622
  68. van Rhijn BW, Lurkin I, Chopin DK, et al. Combined microsatellite and FGFR3 mutation analysis enables a highly sensitive detection of urothelial cell carcinoma in voided urine. Clin Cancer Res. 2003;9:257–263
  69. Bakkar AA, Wallerand H, Radvanyi F, et al. FGFR3 and TP53 gene mutations define 2 distinct pathways in urothelial cell carcinoma of the bladder. Cancer Res. 2003;63:8108–8112
  70. Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005;16:139–149
  71. Hart KC, Robertson SC, Donoghue DJ. Identification of tyrosine residues in constitutively activated fibroblast growth factor receptor 3 involved in mitogenesis, Stat activation, and phosphatidylinositol 3-kinase activation. Mol Biol Cell. 2001;12:931–942
  72. Webster MK, D'Avis PY, Robertson SC, et al. Profound ligand independent kinase activation of fibroblast growth factor receptor 3 by the activation loop mutation responsible for a lethal skeletal dysplasia, thanatophoric dysplasia type II. Mol Cell Biol. 1996;16:4081–4087
  73. Kouhara H, Hadari YR, Spivak-Kroizman T, et al. A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway. Cell. 1997;89:693–702
  74. Agazie YM, Movilla N, Ischenko I, et al. The phosphotyrosine phosphatase SHP2 is a critical mediator of transformation induced by the oncogenic fibroblast growth factor receptor 3. Oncogene. 2003;22:6909–6918
  75. Qu CK, Nguyen S, Chen J, et al. Requirement of Shp-2 tyrosine phosphatase in lymphoid and hematopoietic cell development. Blood. 2001;97:911–914
  76. Lax I, Wong A, Lamothe B, et al. The docking protein FRS2alpha controls a MAP kinase-mediated negative feedback mechanism for signaling by FGF receptors. Mol Cell. 2002;10:709–719
  77. Nowroozi N, Raffioni S, Wang T, et al. Sustained ERK1/2 but not STAT1 or 3 activation is required for thanatophoric dysplasia phenotypes in PC12 cells. Hum Mol Genet. 2005;14:1529–1538
  78. Koksal IT, Yasar D, Dirice E, et al. Differential PTEN protein expression profiles in superficial versus invasive bladder cancers. Urol Int. 2005;75:102–106
  79. Monsonego-Ornan E, Adar R, Rom E, et al. FGF receptors ubiquitination: Dependence on tyrosine kinase activity and role in down-regulation. FEBS Lett. 2002;528:83–89
  80. Lievens PM, Liboi E. The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum. J Biol Chem. 2003;278:17344–17349
  81. Lievens PM, Mutinelli C, Baynes D, et al. The kinase activity of fibroblast growth factor receptor 3 with activation loop mutations affects receptor trafficking and signaling. J Biol Chem. 2004;279:43254–43260
  82. Lievens PM, Roncador A, Liboi E. K644E/M FGFR3 mutants activate Erk1/2 from the endoplasmic reticulum through FRS2 &;α- and PLC γ-independent pathways. J Mol Biol. 2006;357:783–792
  83. Webster M, Donoghue D. Enhanced signaling and morphological transformation by a membrane-localized derivative of the fibroblast growth factor receptor 3 kinase domain. Molecular and Cellular Biology. 1997;17:5739–5747
  84. Isabelle BP, Claire DL, Radvanyi F, et al. Oncogenic properties of the mutated forms of fibroblast growth factor receptor 3b. Carcinogenesis 2006;27:740–7.
  85. Tomlinson DC, Hurst CD, Knowles MA. Knockdown by shRNA identifies S249C mutant FGFR3 as a potential therapeutic target in bladder cancer. Oncogene. 2007;26:5889–5899
  86. Weinstein IB. Cancer (Addiction to oncogenes—the Achilles heel of cancer). Science. 2002;297:63–64
  87. Martinez-Torrecuadrada J, Cifuentes G, Lopez-Serra P, et al. Targeting the extracellular domain of fibroblast growth factor receptor 3 with human single-chain Fv antibodies inhibits bladder carcinoma cell line proliferation. Clin Cancer Res. 2005;11:6280–6290

PII: S1078-1439(10)00188-2

doi: 10.1016/j.urolonc.2010.07.014

« Back Urologic Oncology: Seminars and Original Investigations

Article in Press

Article Tools

* Image Usage & Resolution