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

• Published in: FEBS letters 2012-10, Vol.586 (20), p.3681-3691
• Main Authors: Farina, Antonietta R., Cappabianca, Lucia, Ruggeri, Pierdomenico, Di Ianni, Natalia, Ragone, Marzia, Merolle, Stefania, Sano, Kimihiko, Stracke, Mary L., Horowitz, Jonathan M., Gulino, Alberto, Mackay, Andrew R.
• Format: Article
• Language: English
• Subjects: activating transcription factor; activator protein-1; AP-1; AP1; ATF; Atx; Autotaxin; cAMP response element; Cell Line, Tumor; ChIp; chromatin immunoprecipitation; CRE; CRE binding protein; CREB; Curcumin; Curcumin - pharmacology; Cyclic AMP - genetics; electro-mobility shift assay; EMSA; GAPDH; Gene Deletion; Genes, Reporter - genetics; glyceraldehyde-3-phosphate dehydrogenase; Humans; Internally initiated SP3; Neuroblastoma; Neuroblastoma - pathology; Phosphoric Diester Hydrolases - deficiency; Phosphoric Diester Hydrolases - genetics; Proto-Oncogene Proteins c-myc - metabolism; Response Elements - drug effects; Response Elements - genetics; Sp Transcription Factors - metabolism; specificity protein; Transcription; Transcription Factor AP-1 - metabolism; Transcription, Genetic - drug effects; Transcriptional Activation - drug effects
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2012.08.026

► We report a novel transcriptional mechanism for autotaxin expression in human neuroblastoma cells. ► This mechanism is common to Nmyc amplified and non-amplified neuroblastoma cells. ► This mechanism involves functional CRE/AP-1-like and GA-box elements within the first 285bp of the autotaxin promoter. ► This mechanism depends upon Jun and SP transcription factors. ► This mechanism is inhibited by internally initiated SP-3 and is abrogated by the natural phenol curcumin. 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.