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Employment of microarray analysis to characterize biologic differences associated with tropism-modified adenoviral vectors: utilization of non-native cellular entry pathways

Abstract

In this study, we have applied high-density oligonucleotide microarray technology to characterize biologic changes associated with adenoviral vector-mediated target cell infection. We infected a human melanoma cell line, M21, with the tropism-modified vectors, Ad5lucRGD and Ad5/3luc1. In addition, we infected the M21 cell line with the Ad5luc1, a vector which primarily exploits the coxsackie and adenovirus receptor, as its primary native receptor. We found significant changes in gene expression of 5492 genes induced by Ad5luc1 infection, 2439 genes induced by Ad5/3luc1 infection, and 1251 genes induced by Ad5lucRGD infection, compared to unifected cells. Among these changes in gene expression, 783 changes were common to Ad5/3luc1 and Ad5luc1 infections, 266 were common to Ad5lucRGD and Ad5luc1 infections, and 185 changes in gene expression were common to Ad5/3luc1 and Ad5lucRGD infections. Interestingly, 89 changes in gene expression were common to all the three groups, suggesting a commonly affected pathway. This analysis represents a unique application of microarray to study vector-related issues. Furthermore, these studies demonstrate the utility of microarray for characterizing the biologic sequelae of host–vector interaction.

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Acknowledgements

This work was supported by the following grants from the National Institutes of Health: RO1 HL67962 and RO1 CA86881. We would like to acknowledge Dr Igor Dmitriev and Dr Victor Krasnykh for providing the Ad5luc1, Ad5/3luc1, and Ad5lucRGD adenoviral vectors. Furthermore, we would like to thank Dr John Dubay and Dr Lihong Teng for their technical support, Dr Jode Edwards for assistance with the biostatistical analysis and Dr David Cheresh for contributing the human melanoma cell line M21.

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Correspondence to David T Curiel.

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Volk, A., Rivera, A., Page, G. et al. Employment of microarray analysis to characterize biologic differences associated with tropism-modified adenoviral vectors: utilization of non-native cellular entry pathways. Cancer Gene Ther 12, 162–174 (2005). https://doi.org/10.1038/sj.cgt.7700776

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