title: Cyclooxygenase-2 promoter for tumour-specific targeting of adenoviral vectors to melanoma.
abstract: Novel therapeutic strategies are warranted for the treatment of metastatic melanoma as conventional therapies are inefficient. Conceptually, these strategies should be systemic and tumour-targeted. Gene therapy and viral oncolysis represent promising new approaches for cancer treatment that allow for the incorporation of molecular targeting strategies. In this regard, we analysed cyclooxygenase-2 (cox-2) expression as a potential new target for melanoma gene therapy. By reverse transcription polymerase chain reaction analysis, we showed cox-2 mRNA expression in all of the six tested melanoma cell lines, thus establishing cox-2 as a tumour marker for melanoma of potential interest for targeted therapeutics. Next, we analysed the activity and specificity of the cox-2 promoter within adenoviral vectors by luciferase assays. For this purpose, melanoma cell lines, primary melanoma cells and normal melanocytes were infected with adenoviruses containing cox-2 promoter sequences driving the luciferase reporter gene. The results demonstrated activity of the cox-2 promoter in melanoma cell lines and primary melanoma cells, but not in non-malignant primary epidermal melanocytes. Thus, we established herein the tumour specificity of the cox-2 promoter with potential applications for transcriptional targeting of adenoviral vector-based cancer gene therapy or virotherapy to melanoma.
authors.affiliation: Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. dirk.nettelbeck@derma.imed.uni-erlangen.de
authors.forename: D M
authors.initials: DM
authors.lastname: Nettelbeck
authors.forename: A A
authors.initials: AA
authors.lastname: Rivera
authors.forename: J
authors.initials: J
authors.lastname: Davydova
authors.forename: D
authors.initials: D
authors.lastname: Dieckmann
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: D T
authors.initials: DT
authors.lastname: Curiel
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D051546:Cyclooxygenase 2; D016503:Drug Delivery Systems / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics*; D008565:Membrane Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases