Disease relevance of FGF13

• The FHF2 gene localisation and tissue-specific expression pattern suggest it to be a candidate gene for familial cases of the BFLS syndrome and other syndromal and non-specific forms of X-linked mental retardation mapping to the region [1].
• We have examined the expression of FGF-1 and FGF-2 in a series of 41 colorectal tumours (24 adenomas, 17 adenocarcinomas) and 50 gastric adenocarcinomas (23 intestinal, 27 diffuse), using immunohistochemistry [2].
• The human breast cancer cell lines MCF-7 and MDA-MB-231 differ in their responsiveness to fibroblast growth factor-2 (FGF-2) [3].
• Conversely, FGF-2 expression was reduced in 16 (66 per cent), 8 (47 per cent), and 40 (80 per cent) adenomas and colorectal and gastric samples, respectively [2].
• In a second experiment, HEC-FGF2 human endometrial cancer cells that overexpress fibroblast growth factor-2 were implanted in a hollow fiber placed s.c. in vivo [4].

Psychiatry related information on FGF13

• Hippocampal FGF-2 and FGFR1 mRNA expression in major depression, schizophrenia and bipolar disorder [5].

High impact information on FGF13

• Effects on FGF-2- or vascular endothelial growth factor (VEGF)-stimulated endothelial cell migration, invasion, and tube formation were measured by use of one cell line only (HUVEC) [6].
• Fibroblast growth factor-2 (FGF-2) increases the expression of antiapoptotic proteins, XIAP and Bcl-X(L), and triggers chemoresistance in SCLC cells [7].
• RNAi-mediated downregulation of B-Raf, PKCepsilon or S6K2 abolishes FGF-2-mediated survival [7].
• FGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCepsilon, B-Raf and S6K2 [7].
• Surprisingly, inhibiting the autocrine FGF-2 required for proliferation has no effect on oncogenic Ras-mediated repression of muscle-specific gene expression [8].

Chemical compound and disease context of FGF13

• To investigate the potential regulation of FGF-2 mitogenic activity by heparan sulfate proteoglycans (HSPG), we have treated human breast cancer cells by glycosaminoglycan degrading enzymes or a metabolic inhibitor of proteoglycan sulfation: sodium chlorate [3].
• We previously reported that FGF-1, FGF-2, and heparin are each capable of stimulating megakaryocytopoiesis in vitro and that heparin has a thrombopoietic effect when administered to patients with chronic immune thrombocytopenic purpura [9].
• Human endometrial adenocarcinoma HEC-1-B-derived Tet-FGF-2 cells that express FGF-2 under the control of the tetracycline-responsive promoter (Tet-off system) were further transfected with a VEGF(121) anti-sense (AS-VEGF) cDNA [10].
• These results provide novel finding that ET-AR in PASMCs in vitro is unresponsive to hypoxia per se but is robustly simulated by tyrosine kinase receptor-associated growth factors (FGF-1, FGF-2, PDGF-BB) that themselves are stimulated by hypoxia in lung [11].
• Alliin significantly inhibited both FGF2 and VEGF secretion from human fibrosarcoma cells in a concentration-dependent manner [12].

Biological context of FGF13

• The gene structure of FHF2 was determined and two new exons were identified, including a new 5' end exon, 1B [1].
• Database searches and analysis of available genomic DNA sequence from the region revealed the presence of the fibroblast growth factor homologous factor gene, FHF2, within the duplication breakpoint interval [1].
• Assignment of FGF13 to human chromosome band Xq21 by in situ hybridization [13].
• Addition of survival factors, such as VEGF and FGF-2, does not prevent apoptosis of suspended EC [14].
• The responsiveness to the survival factor activities of VEGF and FGF-2 was not dependent on cell shape changes since it was retained after cytochalasin D treatment [14].

Anatomical context of FGF13

• However, retinal ganglion cells and spinal ventral horn motor neurons show very low levels of FHF2 expression, and their axons exhibit no nodal FHF2 staining within the optic nerve and ventral root, respectively [15].
• Thus, FHF2 is selectively localized at nodes of dorsal root sensory but not ventral root motor axons [15].
• FHF2 is abundantly expressed in the hippocampus and DRG neurons and colocalizes with Na(v)1.6 at mature nodes of Ranvier in myelinated sensory fibers in the dorsal root of the sciatic nerve [15].
• We conclude that oncogenic Ras-induced proliferation of skeletal muscle cells is mediated via a unique and novel mechanism that is distinct from Ras-induced repression of terminal differentiation and involves activation of extracellularly localized, inactive FGF-2 [8].
• Fibroblast growth factor (FGF) 1 and FGF-2 are prototypic members of the FGF family, which to date comprises at least 18 members [16].

Associations of FGF13 with chemical compounds

• Consistent with a role for FHFs as signaling molecules, FHF2 isolated from rat brain is serine/threonine-phosphorylated, and FHF can serve as a substrate for p38delta in vitro [17].
• Oncogenic Ras-induced proliferation is abolished by addition of an anti-FGF-2 blocking antibody, suramin, or treatment with either sodium chlorate or heparitinase, demonstrating an autocrine requirement for FGF-2 [8].
• Cell-surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2 [18].
• Although fibroblast growth factor 1 (FGF-1) (formerly known as acidic FGF) but not FGF-2 (or basic FGF), has been suggested to play a pathophysiological role in liver regeneration, its clinical application has been restricted by its limited mitogenecity and heparin dependence [19].
• We found that low concentrations of the specific Hsp90 inhibitors, geldanamycin and radicicol, completely blocked the translocation of FGF-1 and FGF-2 to the cytosol and the nucleus [20].

Physical interactions of FGF13

• FHF2 also binds weakly to IB2(Delta1-436) and can thereby increase p38delta interaction with IB2(Delta1-436) [17].

Regulatory relationships of FGF13

• In proliferation studies with BaF3 cells, FGF-13 preferentially activates cell clones expressing either FGF receptor variant, 3-IIIc or 4 [21].

Other interactions of FGF13

• FGF-13 is most homologous, 70% similarity at the amino acid level, to FGF-8 [21].
• 1. The SLC9A6 and FGF13 genes in this region, were selected and screened for mutation in this family, but no mutation was detected [22].
• Recently, it has been shown that cells residing in the sub-ventricular zone of adult brains have characteristics of neuronal precursors: they can respond to FGF-2 by proliferation and FGF-1 induces neuronal differentiation [23].

Analytical, diagnostic and therapeutic context of FGF13

• Through a combination of matrix-assisted laser desorption ionization mass spectrometry and chemical crosslinking, we show here that, under identical conditions, FGF-1 and FGF-2 differ in the degree and kind of oligomerization [16].
• Polyclonal primary antibodies (Dr. A. Baird, Whittier Institute, La Jolla, CA) to FGF-1 and FGF-2 and fluorescein-conjugated secondary antibodies were used with confocal microscopy to allow quantitation and subcellular localization of the antigens [24].
• The interaction between FGF-2 and proteoglycans was assayed by examining the binding of 125I-FGF-2 to breast cancer cell cultures as well as to cationic membranes loaded with HSPG [3].
• A novel ELISA based method was developed to detect solubilisation of FGF-2 following addition of heparin and heparitinase to bronchial tissue slices [25].
• A potent fibroproliferative factor in bronchoalveolar lavage fluid in asthma is fibroblast growth factor-2 (FGF-2) [25].

References