Adenovirus-mediated hPNPaseold-35 gene transfer as a therapeutic strategy for neuroblastoma
✍ Scribed by Tom Van Maerken; Devanand Sarkar; Frank Speleman; Paul Dent; William A. Weiss; Paul B. Fisher
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 327 KB
- Volume
- 219
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
Current treatment options for neuroblastoma fail to eradicate the disease in the majority of high‐risk patients, clearly mandating development of innovative therapeutic strategies. Gene therapy represents a promising approach for reversing the neoplastic phenotype or driving tumor cells to self‐destruction. We presently studied the effects of adenovirus‐mediated gene transfer of human polynucleotide phosphorylase (hPNPase^old‐35^), a 3′,5′‐exoribonuclease with growth‐inhibitory properties, in neuroblastoma cells. Transgene expression was driven by either the cytomegalovirus (CMV) promoter or by a tumor‐selective promoter derived from progression elevated gene‐3 (PEG‐3). Our data demonstrate that efficient adenoviral transduction of neuroblastoma cells and robust transgene expression are feasible objectives, that the PEG‐3 promoter is capable of selectively targeting gene expression in the majority of neuroblastoma cells, and that hPNPase^old‐35^ induces profound growth suppression and apoptosis of malignant neuroblastoma cells, while exerting limited effects on normal neural crest‐derived melanocytes. These findings support future applications of hPNPase^old‐35^ for targeted gene‐based therapy of neuroblastoma and suggest that combination with the PEG‐3 promoter holds promise for creating a potent and selective neuroblastoma therapeutic. J. Cell. Physiol. 219: 707–715, 2009. © 2009 Wiley‐Liss, Inc.