Cyclooxygenase-2 promoter for tumour-specific targeting of adenoviral vectors to melanoma.
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| 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.
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| Authors | D M Nettelbeck, A A Rivera, J Davydova, D Dieckmann, M Yamamoto, D T Curiel |
| Journal | Melanoma research (Melanoma Res) Vol. 13 Issue 3 Pg. 287-92 (Jun 2003) ISSN: 0960-8931 [Print] England |
| PMID | 12777984 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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