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Journal of Virology, December 2002, p. 12483-12490, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12483-12490.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Evidence that Replication of the Antitumor Adenovirus ONYX-015 Is Not Controlled by the p53 and p14^ARF Tumor Suppressor Genes

Sara J. Edwards,¹ Brett R. Dix,^1, Colleen J. Myers,¹ Deirdre Dobson-Le,¹ Lily Huschtscha,² Merilyn Hibma,³ Janice Royds,¹ and Antony W. Braithwaite^1*

Departments of Pathology,¹ Microbiology, University of Otago, Dunedin, New Zealand,³ Children's Medical Research Institute, Westmead, Sydney, New South Wales 2145, Australia²

Received 12 June 2002/ Accepted 11 September 2002

The adenovirus mutant ONYX-015 is in phase III clinical trials as a novel antitumor therapy. Its apparent efficacy is thought to be due to its ability to replicate selectively in tumor cells defective in the signaling pathway for p53. Recent data have shown that p14^ARF, a positive regulator of p53, inhibits ONYX-015 replication in cells with a wild-type p53, a phenotype that characterizes normal cells. We, however, found that ONYX-015 activates p53 in tumor cells and in normal cells and that this can occur without p14^ARF induction. We also show that ONYX-015 is not attenuated in cells with functional p53, whether or not p14^ARF is expressed, and that where attenuation does occur, it is cell type specific.

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* Corresponding author. Mailing address: Department of Pathology, University of Otago, Box 913, Dunedin, New Zealand. Phone: 64 3 4797656. Fax: 64 3 4797279. E-mail: antony.braithwaite{at}stonebow.otago.ac.nz.

Present address: School of Pharmacy, Curtin University, Perth, Australia.

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Journal of Virology, December 2002, p. 12483-12490, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12483-12490.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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