title: Induction of Id-1 by FGF-2 involves activity of EGR-1 and sensitizes neuroblastoma cells to cell death.
abstract: Inhibitor of differentiation-1 (Id-1) is a member of helix-loop-helix (HLH) family of proteins that regulate gene transcription through their inhibitory binding to basic-HLH transcription factors. Similarly to other members of this family, Id-1 is involved in the repression of cell differentiation and activation of cell growth. The dual function of Id-1, inhibition of differentiation, and stimulation of cell proliferation, might be interdependent, as cell differentiation is generally coupled with the exit from the cell cycle. Fibroblast growth factor-2 (FGF-2) has been reported to play multiple roles in different biological processes during development of the central nervous system (CNS). In addition, FGF-2 has been described to induce "neuronal-like" differentiation and trigger apoptosis in neuroblastoma SK-N-MC cells. Although regulation of Id-1 protein by several mitogenic factors is well-established, little is known about the role of FGF-2 in the regulation of Id-1. Using human neuroblastoma cell line, SK-N-MC, we found that treatment of these cells with FGF-2 resulted in early induction of both Id-1 mRNA and protein. The induction occurs within 1 h from FGF-2 treatment and is mediated by ERK1/2 pathway, which in turn stimulates expression of the early growth response-1 (Egr-1) transcription factor. We also demonstrate direct interaction of Egr-1 with Id-1 promoter in vitro and in cell culture. Finally, inhibition of Id-1 expression results in G(2) /M accumulation of FGF-2-treated cells and delayed cell death.
authors.affiliation: Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Passiatore
authors.forename: Antonio
authors.initials: A
authors.lastname: Gentilella
authors.forename: Slava
authors.initials: S
authors.lastname: Rom
authors.forename: Marco
authors.initials: M
authors.lastname: Pacifici
authors.forename: Valeria
authors.initials: V
authors.lastname: Bergonzini
authors.forename: Francesca
authors.initials: F
authors.lastname: Peruzzi
mesh_terms: D017209:Apoptosis; D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3