Disease relevance of FGF6

• Fourteen of 26 prostate cancers expressed FGF6 mRNA [1].
• The mRNAs for the other four members of the fibroblast growth factor (FGF) family, including acidic FGF, int-2 protein, hst-1 protein, FGF5 protein and FGF6/hst-2 protein could not be detected in the esophageal and gastric cancer cell lines [2].
• Plasmid and adenovirus vectors immobilized in collagen-gelatin admixtures were delivered to excisional muscle wounds, and when encoding either fibroblast growth factor-2 (FGF2) or FGF6 transgenes, produced early angiogenic responses that subsequently remodeled into arteriogenesis [3].
• Recent reports support the concept that FGF6 has a dual function in muscle regeneration, stimulating myoblast proliferation/migration and muscle differentiation/hypertrophy in a dose-dependent manner [4].
• The resulting construct is able to drive the expression of a high amount of FGF-6 protein in Escherichia coli, which can be solubilized and purified through heparin-Sepharose chromatography and high salt elution [5].

High impact information on FGF6

• Fibroblast growth factor 6 gene expression in AIDS-associated Kaposi's sarcoma [6].
• In addition, FGF-6 was found to bind to FGFR-4 in ligand competition experiments [7].
• FGF receptor 4, which is the most potent FGF receptor for FGF6, is expressed in the human prostate in vivo and in all of the cultured cell lines [1].
• Exogenous FGF6 was able to stimulate proliferation of primary prostatic epithelial and stromal cells, immortalized prostatic epithelial cells, and prostate cancer cell lines in tissue culture [1].
• An ELISA of tissue extracts of normal prostate, high-grade prostatic intraepithelial neoplasia (PIN), and prostate cancer for FGF6 showed that this growth factor was undetectable in normal prostate but was present at elevated levels in 4 of 9 PIN lesions and in 15 of 24 prostate cancers [1].

Biological context of FGF6

• Intergenic conserved region (IGCR) within the FGF6-FGF23 gene cluster was identified based on the evolutionary conservation [8].
• Nucleotide sequence analysis of the FGF6 gene and of cDNA clones revealed an open reading frame able to code for a protein of 208 residues [9].
• Nutritional status significantly influenced the myostatin expression levels in muscle, inducing an up-regulation during fasting and a down-regulation during the recovery from fasting, whereas the muscular FGF6 mRNA levels were not significantly affected by the feeding status of the animals [10].
• FGF6 in myogenesis [4].
• Moreover, principal component analysis made it possible to distinguish specific contributions of either FGF6 or differentiation effects on gene expression profiles [11].

Anatomical context of FGF6

• Thus, FGF6 is increased in PIN and prostate cancer and can promote the proliferation of the transformed prostatic epithelial cells via paracrine and autocrine mechanisms [1].
• We show here that DT/FGF6 targets myoblasts engineered to express either one of the four FGFR, as well as FGFR-expressing tumour cells [12].
• In-vitro analysis indicates that this signal peptide is able to drive the FGF6 protein through the endoplasmic reticulum, where it becomes glycosylated [9].
• We also report on the expression profile of myostatin and FGF6 in sea bass skeletal muscle in response to different feeding regimens, as quantified by real-time RT-PCR [10].
• Important functions in myogenesis have been proposed for FGF6, a member of the fibroblast growth factor family accumulating almost exclusively in the myogenic lineage [4].

Associations of FGF6 with chemical compounds

• The reverse, however, was the case for the HST2 isoforms, particularly HST2b, which preferentially sulfonated cholesterol and oxysterols, in contrast to DHEA, which served as a poor substrate for this enzyme [13].
• This conserved histidine (His-135 in HST2) activates the ribose 2'-hydroxyl for attack on the alpha-1'-O-alkylamidate [14].

Other interactions of FGF6

• In addition to the myeloid-specific genes, other over-expressed genes included AML1, LCP2 and FGF6 [15].
• The second cell line, GM01203A, exhibits a balanced t(4;12)(4q25; 12p13.3) with a breakpoint between FGF6 and D12S370 [16].
• It was particularly notable that both HST2 isoforms, but not HST1, were expressed in skin, a tissue where cholesterol sulfonation plays an important role in normal development of the skin barrier [13].
• The open reading frames of myostatin (376 amino acids) and FGF6 (209 amino acids) showed 97-63% and 87-62% sequence identity with other vertebrate myostatins and FGF6s, respectively [10].
• In order to study more thoroughly the activities of FGF-6, we have constructed a bacterial expression vector by inserting FGF-6 complementary DNA sequences into the T7 RNA polymerase-based pET3a vector [5].

Analytical, diagnostic and therapeutic context of FGF6

• Like flg, bek was expressed in all tissue samples and KS-derived cell cultures except in one KS specimen obtained from the patient's tongue showing expression of a high level of FGF-6 [17].

References