Cell responses to FGFR3 signalling:: growth, differentiation and apoptosis

被引:166
作者
L'Hôte, CGM [1 ]
Knowles, MA [1 ]
机构
[1] St James Univ Hosp, Canc Res UK Clin Ctr, Leeds LS9 7TF, W Yorkshire, England
关键词
FGFR3; FGF; splice; mutation; achondroplasia; multiple myeloma; bladder cancer; signalling; STAT;
D O I
10.1016/j.yexcr.2004.11.012
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
FGFR3 is a receptor tyrosine kinase (RTK) of the FGF receptor family, known to have a negative regulatory effect on long bone growth. Fgfr3 knockout mice display longer bones and, accordingly, most germline-activating mutations in man are associated with dwarfism. Somatically, some of the same activating mutations are associated with the human cancers multiple myeloma, cervical carcinoma and carcinoma of the bladder. How signalling through FGFR3 can lead to either chondrocyte apoptosis or cancer cell proliferation is not fully understood. Although FGFR3 can be expressed as two main splice isoforms (IIIb or IIIc), there is no apparent link with specific cell responses, which may rather be associated with the cell type or its differentiation status. Depending on cell type, differential activation of STAT proteins has been observed. STAT1 phosphorylation seems to be involved in inhibition of chondrocyte proliferation while activation of the ERK pathway inhibits chondrocyte differentiation and B-cell proliferation (as in multiple myeloma). The role of FGFR3 in epithelial cancers (bladder and cervix) is not known. Some of the cell specificity may arise via modulation of signalling by crosstalk with other signalling pathways. Recently, inhibition of the ERK pathway in achondroplastic mice has provided hope for an approach to the treatment of dwarfism. Further understanding of the ability of FGFR3 to trigger different responses depending on cell type and cellular context may lead to treatments for both skeletal dysplasias and cancer. (c) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:417 / 431
页数:15
相关论文
共 145 条
  • [81] Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity
    Olsen, SK
    Ibrahimi, OA
    Raucci, A
    Zhang, FM
    Eliseenkova, AV
    Yayon, A
    Basilico, C
    Linhardt, RJ
    Schlessinger, J
    Mohammadi, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (04) : 935 - 940
  • [82] Mutation, SNP, and isoform analysis of fibroblast growth factor receptor 3 (FGFR3) in 150 newly diagnosed multiple myeloma patients
    Onwuazor, ON
    Wen, XY
    Wang, DY
    Zhuang, LH
    Masih-Khan, E
    Claudio, J
    Barlogie, B
    Shaughnessy, JD
    Stewart, AK
    [J]. BLOOD, 2003, 102 (02) : 772 - 773
  • [83] Differential effects of heparin saccharides on the formation of specific fibroblast growth factor (FGF) and FGF receptor complexes
    Ostrovsky, O
    Berman, B
    Gallagher, J
    Mulloy, B
    Fernig, DG
    Delehedde, M
    Ron, D
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (04) : 2444 - 2453
  • [84] Passos-Bueno MR, 1999, HUM MUTAT, V14, P115
  • [85] DIFFERENT MEMBERS OF THE FIBROBLAST GROWTH-FACTOR RECEPTOR FAMILY ARE SPECIFIC TO DISTINCT CELL-TYPES IN THE DEVELOPING CHICKEN-EMBRYO
    PATSTONE, G
    PASQUALE, EB
    MAHER, PA
    [J]. DEVELOPMENTAL BIOLOGY, 1993, 155 (01) : 107 - 123
  • [86] Bladder cancer
    Patton, SE
    Hall, MC
    Ozen, H
    [J]. CURRENT OPINION IN ONCOLOGY, 2002, 14 (03) : 265 - 272
  • [87] Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin
    Pellegrini, L
    Burke, DF
    von Delft, F
    Mulloy, B
    Blundell, TL
    [J]. NATURE, 2000, 407 (6807) : 1029 - 1034
  • [88] UNIQUE EXPRESSION PATTERN OF THE FGF RECEPTOR-3 GENE DURING MOUSE ORGANOGENESIS
    PETERS, K
    ORNITZ, D
    WERNER, S
    WILLIAMS, L
    [J]. DEVELOPMENTAL BIOLOGY, 1993, 155 (02) : 423 - 430
  • [89] Fgfr3 expression by astrocytes and their precursors:: evidence that astrocytes and oligodendrocytes originate in distinct neuroepithelial domains
    Pringle, NP
    Yu, WP
    Howell, M
    Colvin, JS
    Ornitz, DM
    Richardson, WD
    [J]. DEVELOPMENT, 2003, 130 (01): : 93 - 102
  • [90] Activation of the ERK1/2 and p38 mitogen-activated protein kinase pathways mediates fibroblast growth factor-induced growth arrest of chondrocytes
    Raucci, A
    Laplantine, E
    Mansukhani, A
    Basilico, C
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (03) : 1747 - 1756