PMID: 15375610Sep 18, 2004Paper

Limited specificity of promoter constructs for gene therapy in osteosarcoma

International Journal of Molecular Medicine
Annika PollmannOlaf J C Hellwinkel

Abstract

Osteosarcoma (OS), a malignant bone neoplasia in childhood, has poor prognosis if metastases appear in the lung. A novel therapeutic approach could consist in a gene therapeutic treatment of OS metastases. However, if promiscuous viral vectors are applied for the delivery of potentially toxic transgenes, their misdelivery into normal tissues could cause severe complications. This problem could be circumvented by application of OS-specific promoters for transgene expression control. We analysed the function of promoters described to be tumour-, osteosarcoma- or osteoblast-specific. Expression rates driven by osteoblast- specific fragments from the collagen1A1-promoter, the human Osteocalcin-promoter, the bone-sialoprotein promoter and the beta-catenin promoter depending on vitamin supplementation were analysed in five OS cell lines, in normal lung fibroblasts and in a non-osteoblastic prostate cancer cell line (LNCaP) by dual luciferase assays. In addition, an unspecific but doxycyclin-repressible promoter construct (pAd.3r-luc) was examined. We found that all constructs were active in OS cell lines to varying extents. The complete human Osteocalcin promoter and the bone-sialoprotein promoter were partially induced by vitamin D3...Continue Reading

Citations

Apr 3, 2008·The Journal of Pharmacy and Pharmacology·Crispin R Dass, Peter F M Choong
May 3, 2007·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Joohee JungShun'ichi Kuroda

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