Disease relevance of FGF10

• However, unlike the Apert syndrome Pro253Arg FGFR2c mutant, neither the Pfeiffer syndrome Pro250Arg FGFR1c mutant nor the Muenke syndrome Pro250Arg FGFR3c mutant bound appreciably to FGF7 or FGF10 [1].
• All five colorectal cancer cell lines expressed FGF-10 mRNA and its protein [2].
• These findings indicate that FGF-10 and its receptor, FGFR2 iiib expression in colorectal adenocarcinoma cells and FGF-10 may contribute to the growth of cells of this type [2].
• Our current study was designed to examine the local production and action of two specific stromal-epithelial cell mediatory factors, keratinocyte growth factor (KGF) and FGF-10, in human endometrial carcinoma cells [3].
• Immunohistochemical analysis of keratinocyte growth factor and fibroblast growth factor 10 expression in psoriasis [4].

High impact information on FGF10

• FGF7 and FGF10 activate only the b isoform of FGFR2 (FGFR2b) [5].
• Structure-based mutagenesis of FGF10 confirms the importance of the observed contacts for FGF10 biological activity [5].
• Unique contacts between divergent regions in FGF10 and two b-specific loops in D3 reveal the structural basis by which alternative splicing provides FGF10-FGFR2b specificity [5].
• In some cases, marked HOX overexpression was associated with elevated FGF10 and FGF17 [6].
• Highly similar lung and limb phenotypes were detected recently in the loss of function mutation of Fgf10, a ligand of Fgfr2 [7].

Chemical compound and disease context of FGF10

• Human FGF-10 (amino acids 40 to 208 with a methionine residue at the amino terminus) was produced in Escherichia coli and purified from the cell lysate [8].

Biological context of FGF10

• Among the FGFs, FGF7 and FGF10 have been implicated in the regulation of prostate development and prostate tissue homeostasis by signaling through the FGFR2 isoform [9].
• In both Fgf10 and Fgfr2 deficient mutant hypospadic male mice, cell proliferation is arrested prematurely and the maturation of the urethral epithelium is disrupted [10].
• First trimester fetal lung explants developed dose-dependent increases in intraluminal volume in response to KGF and FGF-10 [11].
• FGF-10 is known to play an important role in fetal limb and lung development, skin wound healing and prostatic epithelial cell growth [2].
• The ratio of bud increment of each cultured lung was calculated, and the FGF10 and BMP4 mRNA expression levels were analyzed by real-time reverse transcription polymerase chain reaction [12].

Anatomical context of FGF10

• RESULTS: FGF10 is expressed at levels detectable by RT-PCR and can act as a growth factor for prostatic epithelial cells, but is not active as a growth factor for stromal cells [13].
• By using in situ hybridization, FGF-10 mRNA was observed in colorectal cancer cells and fibroblasts adjacent to cancer cells [2].
• This method allowed us to demonstrate that human embryonic pancreatic mesenchyme expresses FGF7 and FGF10 that act on epithelial cells to activate their proliferation [14].
• RESULTS: We found that different FGFs are expressed in the human embryonic pancreas, and we focused on FGF7 and FGF10 [14].
• The aim of this study was to investigate the expression of KGF and FGF-10 on the skin of patients with psoriasis by immunohistochemical analysis and to evaluate the correlation with the lymphocyte infiltrate and the epidermal proliferation [4].

Associations of FGF10 with chemical compounds

• There was a significant increase in BMP4 mRNA expression in 100 micromol/L DETA/NO (190% +/- 20%) compared to controls (100% +/- 30%) (P < .05), whereas FGF10 mRNA expression was not significantly different between each DETA/NO group and controls [12].
• Blocking the MAPK pathway with the specific methyl ethyl ketone 1/2 inhibitor (U0126) completely neutralized the enhancement of cell proliferation induced by KGF and FGF-10 [3].
• Both fibroblast growth factor 10 and keratinocyte growth factor bind with high affinity to the tyrosine kinase keratinocyte growth factor receptor [15].
• Both dermal and leukemic mast cells expressed fibroblast growth factor 2, fibroblast growth factor 7, and heparin-binding epidermal growth factor, but not hepatocyte growth factor at mRNA level, and dermal mast cells expressed fibroblast growth factor 10 in addition [16].
• We show that FGF-10 prevents H2O2-induced DNA damage assessed by an alkaline elution, ethidium bromide fluorescence as well as by a comet assay [17].

Regulatory relationships of FGF10

• However, FGF10 is expressed at extremely low levels relative to FGF7, which has a similar biological activity [13].
• KGF and FGF-10 could induce the prompt phosphorylation of ERK1/2 and consequently stimulate DNA synthesis [3].
• We conclude that FGF-10 attenuates H2O2-induced AEC DNA damage by mechanisms that involve activation of Grb2-SOS/Ras/RAF-1/ERK1/2 pathway and DNA repair [17].
• Fibroblast growth factor-10 prevents H(2)O(2)-induced cell cycle arrest by regulation of G1 cyclins and cyclin dependent kinases [18].
• FGF-10 prevented H(2)O(2)-induced upregulation of CDK inhibitor, p21 [18].

Other interactions of FGF10

• We have compared the sequences of the nine known mammalian FGFs, FGFs from other vertebrates, and three additional sequences that we extracted from existing databases: two human FGF sequences that we tentatively designated FGF10 and FGF11, and an FGF sequence from Caenorhabditis elegans [19].
• EGF and basic FGF, but not FGF4 and FGF10, increased Sprouty-2 mRNA expression in GLC [20].
• We hypothesized that fibroblast growth factor-10 (FGF-10) and fibroblast growth factor receptors 1-4 (FGFR 1-4) are expressed in human decidual and placental tissues [21].
• Activation of mitogen-activated protein kinase pathway by keratinocyte growth factor or fibroblast growth factor-10 promotes cell proliferation in human endometrial carcinoma cells [3].
• Based on our data, we propose that an increase in mutant FGFR2c binding to multiple FGFs results in craniosynostosis, whereas binding of mutant FGFR2c to FGF10 results in severe limb pathology [22].

Analytical, diagnostic and therapeutic context of FGF10

• To determine the localization of FGF-10 protein and its mRNA in normal and cancerous human colorectal tissues, immunohistochemistry and in situ hybridization were performed [2].
• Loss of resident epithelial cell FGFR2IIIb that responds to stromal FGF7 and FGF10 accompanies malignant progression of both model animal and human prostate tumors [23].
• KGF and FGF-10 did not activate the phosphorylation of Akt, protein kinase C, or signal transducer and activator of transcription-3 [3].
• Microarray analysis of trigeminal ganglia from individual transgenic founders effectively excludes the cell-autonomous activity of FGF10 as a mechanism for mediating the downstream effects of the loss of Brn3a, probably because developing sensory neurons lack the appropriate type of FGF receptor [24].
• Immunoprecipitation/western blot analysis revealed that fibroblast growth factor 10, similarly to keratinocyte growth factor, is able to induce tyrosine phosphorylation of keratinocyte growth factor receptor and of cellular substrates such as PLCgamma [15].

References