title: Synergy between 5' and 3' flanking regions of the human tyrosine hydroxylase gene ensures specific, high-level expression in neuroblastoma cells.
abstract: Factors regulating tyrosine hydroxylase (TH) gene transcription are of major importance in the studies of malignant and degenerative diseases of catecholamine-synthesizing tissues. In this study, we used transient transfection of a reporter gene to show that high-level, tissue-specific TH expression was only achieved when the reporter gene was cloned between a 5' TH promoter sequence (-513-+1), and, a 3' TH gene flanking sequence (end of exon 14-+976). We also show that TH mRNA expression level is closely linked to the expression level of the proto-oncogene, MYCN in neuroblastoma tumor cell lines. Taken together our data indicate that MYCN may regulate TH expression in neuroblastoma cells, but not through binding to the 5' or 3' TH gene flanking sequences used in our experiments.
authors.affiliation: Children's Cancer Institute Australia for Medical Research, NSW, Randwick, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Gardaneh
authors.forename: J
authors.initials: J
authors.lastname: Gilbert
authors.forename: M
authors.initials: M
authors.lastname: Haber
authors.forename: M D
authors.initials: MD
authors.lastname: Norris
authors.forename: S L
authors.initials: SL
authors.lastname: Cohn
authors.forename: M L
authors.initials: ML
authors.lastname: Schmidt
authors.forename: G M
authors.initials: GM
authors.lastname: Marshall
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D020121:5' Untranslated Regions / Q000235:genetics*; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009447:Neuroblastoma / Q000201:enzymology* / Q000473:pathology; D009928:Organ Specificity / Q000235:genetics; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014446:Tyrosine 3-Monooxygenase; D015500:Chloramphenicol O-Acetyltransferase