Fibroblast growth factor receptor-4 shows novel features in genomic structure, ligand binding and signal transduction.

Vainikka, Satu; Partanen, Juha; Bellosta, Paola; Coulier, François; Birnbaum, Daniel; Basilico, Claudio; Jaye, Michael; Alitalo, Kari

doi:10.1002/j.1460-2075.1992.tb05526.x

Cited by 158 publications

(94 citation statements)

References 42 publications

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“…Among the four receptors, FGFR-1 and 2 have a high a nity for FGF-2 (Dionne et al, 1990). In contrast, FGFR-3 preferentially binds FGF-1 (Ornitz and Leder, 1992), and FGFR-4 binds FGF-1 with high a nity but shows low a nity for FGF-2 (Vainikka et al, 1992). Cell transformation upon FGF-2 addition has been described in ®broblasts overexpressing FGFR-1 (Bernard et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of vascular endothelial growth factor induces cell transformation in cooperation with fibroblast growth factor 2

et al. 1997

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Section: Discussionmentioning

confidence: 99%

Overexpression of vascular endothelial growth factor induces cell transformation in cooperation with fibroblast growth factor 2

et al. 1997

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“…FGFRlIIIb binds efficiently to aFGF, FGF3 and FGF 10, while FGFRl Ilk binds to aFGF, bFGF, FGF4, FGF6, FGF8 and FGF9 (Ornitz et al, 1996). FGFRl-3 demonstrate both IIIb and IIIc splice variant isoforms, but FGFR4 is unique and has no IIIb splice variant, being expressed as the IIIc isoform only (Johnson et al, 1991;Vainikka et al, 1992;Chellaiah et al, 1994).…”

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confidence: 99%

Evaluation of the fibroblast growth factor system as a potential target for therapy in human prostate cancer

et al. 2005

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Overexpression of fibroblast growth factors (FGFs) has been implicated in prostate carcinogenesis. FGFs function via their high-affinity interactions with receptor tyrosine kinases, FGFR1 -4. Expression of FGFR1 and FGFR2 in prostate cancer (CaP) was not found to be associated with clinical parameters. In this report, we further investigated for abnormal FGFR expression in prostate cancer and explore their significance as a potential target for therapy. The expression levels of FGFR3 and FGFR4 in CaP were examined and corroborated to clinical parameters. FGFR3 immunoreactivity in benign prostatic hyperplasia (BPH) and CaP (n ¼ 26 and 57, respectively) had similar intensity and pattern. Overall, FGFR4 expression was significantly upregulated in CaP when compared to BPH. A significant positive correlation between FGFR4 expression and Gleason score was noted: Gleason score 7 -10 tumours compared to BPH (Po0.0001, Fisher's exact test), Gleason score 4 -6 tumours compared to BPH (Po0.0004), and Gleason 7 -10 compared to Gleason 4 -6 tumours (Po0.005). FGFR4 overexpression was associated with an unfavourable outcome with decreased disease-specific survival (Po0.04, log rank test). FGF-induced signalling is targeted using soluble FGF receptor (sFGFR), potent inhibitor of FGFR function. We have previously shown that sFGFR expression via a replication-deficient adenoviral vector (AdlllcRl) suppresses in vitro FGF-induced signalling and function in human CaP DU145 cells. We tested the significance of inhibiting FGF function along with conventional therapeutic modalities in CaP, and confirmed synergistic effects on in vitro cell growth (proliferation and colony formation) by combining sFGFR expression and treatment with either Paclitaxel (Taxol s ) or g-irradiation. In summary, our data support the model of FGF system as valid target for therapy in CaP. Prostate cancer is the commonest cancer in men and the second commonest cause of cancer-related death in men, and its incidence is increasing (Woolf, 1995;Boyle et al, 1996). Prostate cancer is an enigmatic disease. It is histologically present in 80% of men over the age of 80 years, but will only clinically manifest itself in about 10%. Increasing use of serum measurement of prostate-specific antigen is facilitating early diagnosis of prostate cancer. There are currently limited prognostic markers that may allow patients found to have early prostate cancer to be stratified into different management plans. Hence, new methods of predicting disease progression are urgently needed.Abnormal expression of peptide growth factors and their highaffinity receptor tyrosine kinases are important in the development and progression of prostate cancer. These mitogens enhance tumour proliferation and invasion while inhibiting apoptosis. Several peptide growth factors have been implicated in prostate cancer development and progression, including insulin-like growth factors, epidermal growth factor and members of the fibroblast growth factors (Byrne et al, 1996;Tennant et al, 1996;Dorkin et...

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“…We don't know the level of expression of FGFR-3 or -4 in these two cell lines but it should be underlined that these two FGF receptors would not contribute to bind FGF-2 e ciently. In fact, FGFR-3/IIIb, the only FGFR-3 variant expressed by the epithelial cells binds only FGF-1 (Chellaiah et al, 1994), while FGFR-4 binds FGF-1 with high a nity but shows low a nity for FGF-2 (Vainikka et al, 1992). Along this line, we have observed that when NBT-II cells, stably transfected with expression vector encoding the human FGFR-1 (WennstroÈ m et al, 1991) or the human IIIc variant of the FGFR-2 (Houssaint et al, 1990), were treated with exogenous FGF-2, they showed a mixture of IIIb and IIIc transcripts and they became dissociated (our unpublished observation).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the FGFR-4 gene was shown to lack two alternative exons for Ig domain 3 and to contain only exon IIIc. This FGFR-4 binds FGF-1 with high a nity but shows low a nity for FGF-2 (Vainikka et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Exon III splicing switch of fibroblast growth factor (FGF) receptor-2 and -3 can be induced by FGF-1 or FGF-2

Scotet

Houssaint

1998

Oncogene

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An essential feature of ®broblast growth factor receptors (FGFRs) is the existence of multiple possibilities of alternative splicing. One of these concerns sequences of the mRNA coding for the C-terminal half of Ig domain 3 which corresponds to a part of the ligand-binding site: two alternative exons, IIIb and IIIc, encode the Cterminal half of Ig domain 3. The IIIb/IIIc choice in the FGFR-2 and FGFR-3 is strictly tissue-speci®c, the IIIb exon being expressed exclusively in epithelial cells. We describe here a reversible switch from IIIb to IIIc for FGFR-2 and FGFR-3 under the in¯uence of exogenous and endogenous FGF-1 or FGF-2. We observed that FGF-induced FGF receptor exon switching (i) occurred as early as 1 h after exposure to FGF (ii) was receptormediated (iii) was dependent on cell con¯uency and showed a link with the cell cycle (iv) was correlated with a reversible loss of epithelial properties. These results support a role for FGF in the regulation of expression of alternatively spliced FGFR mRNA.

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Fibroblast growth factor receptor-4 shows novel features in genomic structure, ligand binding and signal transduction.

Cited by 158 publications

References 42 publications

Overexpression of vascular endothelial growth factor induces cell transformation in cooperation with fibroblast growth factor 2

Overexpression of vascular endothelial growth factor induces cell transformation in cooperation with fibroblast growth factor 2

Evaluation of the fibroblast growth factor system as a potential target for therapy in human prostate cancer

Exon III splicing switch of fibroblast growth factor (FGF) receptor-2 and -3 can be induced by FGF-1 or FGF-2

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