title: Expression of core binding factor alpha1 up-regulated by IGF-I, GM-CSF, and EGF through MAPK pathway in MC3T3-E1 and C2C12 cells.
abstract: OBJECTIVE
  To study the regulating function and mechanism of insulin-like growth factor-I (IGF-I), granulocyte-macrophage colony-stimulating factor (GM-CSF), and epidermal growth factor (EGF) on murine core binding factor alpha1 (Cbfalpha1) gene expression.
  
  
  METHODS
  Luciferase reporter gene method and RT-PCR technique were used to examine the effects of these growth factors on the promoter activity and mRNA expression of Cbfalpha1 gene in MC3T3-E1 and C2C12 cells.
  
  
  RESULTS
  IGF-I (from 1 nmol/L to 1 micromol/L), GM-CSF (100 nmol/L), and EGF (1 micromol/L) increased the luciferase expression in MC3T3-E1 cells (P<0.05). And mitogen-activated protein kinase (MAPK) inhibitor, PD 98059 (10 micromol/L), completely blocked IGF-1, GM-CSF, and EGF-induced expression of Cbfa1 promoter activity (P<0.01). In C2C12 cells, IGF-I (from 1 nmol/L to 10 micromol/L), GM-CSF (100 nmol/L and 1 micromol/L), and EGF (100 nmol/L) enhanced the expression of luciferase reporter plasmid driven by mCbfalpha1 promoter (P<0.05). Addition of PD 98059 also blocked the stimulatory effects of these growth factors on Cbfalpha1 promoter activity (P<0.01). Moreover, Cbfalpha1 mRNA expression was significantly increased after treatment with IGF-I (1 nmol/L, 100 nmol/L), GM-CSF (100 nmol/L, 1 micromol/L), and EGF (1 micromol/L, 100 nmol/L) in MC3T3-E1 and C2C12 cells, respectively (P<0.05). These stimulatory effects of IGF-I, GM-CSF, and EGF on Cbfalpha1 mRNA expression were abolished by PD 98059.
  
  
  CONCLUSIONS
  IGF-I, GM-CSF, and EGF could increase the promoter activity and the mRNA expression of murine Cbfalpha1 gene in MC3T3-E1 and C2C12 cells. These stimulatory effects might be mediated by activating the intracellular MAPK-dependent signaling pathway.
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Pei
authors.forename: Xun-Wu
authors.initials: XW
authors.lastname: Meng
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Zhou
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Xing
authors.forename: Wei-Bo
authors.initials: WB
authors.lastname: Xia
mesh_terms: D000818:Animals; D002460:Cell Line; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D005419:Flavonoids; D012333:RNA, Messenger; D014157:Transcription Factors; C406688:core binding factor alpha; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one