title: Constitutive autotaxin transcription by Nmyc-amplified and non-amplified neuroblastoma cells is regulated by a novel AP-1 and SP-mediated mechanism and abrogated by curcumin.
abstract: The motility, angiogenesis and metastasis-stimulating factor Autotaxin (Atx), over expressed by human neuroblastomas (NB), is constitutively expressed by human Nmyc-amplified SK-N-BE and non-Nmyc-amplified SH-SY5Y NB cells. Here, we characterise a novel Atx transcriptional mechanism, utilised by both cell lines, that is restricted to the first 285bp of the Atx promoter and involves AP-1 and SP transcription factors, acting through a CRE/AP-1-like element at position -142 to -149 and a GAbox at position -227 to -235 relative to the Atx translational start site. This novel transcriptional mechanism can be inhibited by internally initiated SP-3 and the natural phenol curcumin.
authors.affiliation: Section of Molecular Pathology, Department of Experimental Medicine, University of L'Aquila, 67100 L'Aquila, Italy.
authors.forename: Antonietta R
authors.initials: AR
authors.lastname: Farina
authors.forename: Lucia
authors.initials: L
authors.lastname: Cappabianca
authors.forename: Pierdomenico
authors.initials: P
authors.lastname: Ruggeri
authors.forename: Natalia
authors.initials: N
authors.lastname: Di Ianni
authors.forename: Marzia
authors.initials: M
authors.lastname: Ragone
authors.forename: Stefania
authors.initials: S
authors.lastname: Merolle
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Sano
authors.forename: Mary L
authors.initials: ML
authors.lastname: Stracke
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Horowitz
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Mackay
mesh_terms: D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000235:genetics; D017353:Gene Deletion; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D010727:Phosphoric Diester Hydrolases / Q000172:deficiency / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D020218:Response Elements / Q000187:drug effects / Q000235:genetics; D051703:Sp Transcription Factors / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation / Q000187:drug effects; D000099189:Lysophospholipase D
chemical_list: D003474:Curcumin; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D016271:Proto-Oncogene Proteins c-myc; D051703:Sp Transcription Factors; D018808:Transcription Factor AP-1; D000099189:Lysophospholipase D