title: Fibroblast growth factor-2 up-regulates the expression of nestin through the Ras-Raf-ERK-Sp1 signaling axis in C6 glioma cells.
abstract: Nestin is a 240-kDa intermediate filament protein expressed mainly in neural and myogenic stem cells. Although a substantial number of studies have focused on the expression of nestin during development of the central nervous system, little is known about the factors that induce and regulate its expression. Fibroblast growth factor-2 (FGF-2) is an effective mitogen and stimulates the proliferation and differentiation of a subset of nestin-expressing cells, including neural progenitor cells, glial precursor cells, and smooth muscle cells. To assess whether FGF-2 is a potent factor that induces the expression of nestin, C6 glioma cells were used. The results showed that nestin expression was up-regulated by FGF-2 via de novo RNA and protein synthesis. Our RT-PCR results showed that C6 glioma cells express FGFR1/3, and FGFRs is required for FGF-2-induced nestin expression. Further signaling analysis also revealed that FGF-2-induced nestin expression is mediated through FGFR-MAPK-ERK signaling axis and the transcriptional factor Sp1. These findings provide new insight into the regulation of nestin in glial system and enable the further studies on the function of nestin in glial cells.
authors.affiliation: Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Kai-Wei
authors.initials: KW
authors.lastname: Chang
authors.forename: Yuan-Li
authors.initials: YL
authors.lastname: Huang
authors.forename: Zong-Ruei
authors.initials: ZR
authors.lastname: Wong
authors.forename: Peng-Han
authors.initials: PH
authors.lastname: Su
authors.forename: Bu-Miin
authors.initials: BM
authors.lastname: Huang
authors.forename: Tsai-Kai
authors.initials: TK
authors.lastname: Ju
authors.forename: Hsi-Yuan
authors.initials: HY
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D064231:Nestin; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D048490:raf Kinases / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D011758:Pyrroles; C105686:SU 5402; D016329:Sp1 Transcription Factor; D016222:Fibroblast Growth Factor 2; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D018631:ras Proteins