This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cascalló, M. Articles by Alemany, R. Search for Related Content PubMed PubMed Citation Articles by Cascalló, M. Articles by Alemany, R.

Ras-dependent Oncolysis with an Adenovirus VAI Mutant

Translational Research Laboratory, Institut Català d’Oncologia, 08907, L'Hospitalet [M. C., G. C., R. A.], and Department of Biochemistry and Molecular Biology, University of Barcelona 08028 [A. M.], Barcelona, Spain

Adenovirus synthesize proteins that interact with oncogene and tumor suppressor gene products to set the cell for virus replication. Mutant viruses defective in these functions replicate selectively in cancer cells and represent new tools to treat cancer. We report a selectivity strategy based on deletions of adenovirus Virus-Associated (VA) RNAs. In normal cells, these RNAs are necessary for virus replication because they inactivate the RNA-dependent protein kinase protein kinase R, a kinase that otherwise would block protein translation in response to infection. However, downstream effectors of Ras can also inactivate protein kinase R, and therefore, the need for VA RNA genes should be bypassed in cells with an active Ras pathway. We demonstrate here that a VAI RNA mutant presents a Ras-dependent replication and can be used for oncolytic virotherapy of pancreatic tumors.

This article has been cited by other articles:

				S. M. Battcock, T. W. Collier, D. Zu, and K. Hirasawa Negative Regulation of the Alpha Interferon-Induced Antiviral Response by the Ras/Raf/MEK Pathway J. Virol., May 1, 2006; 80(9): 4422 - 4430. [Abstract] [Full Text] [PDF]

				O. Aparicio, N. Razquin, M. Zaratiegui, I. Narvaiza, and P. Fortes Adenovirus Virus-Associated RNA Is Processed to Functional Interfering RNAs Involved in Virus Production J. Virol., February 1, 2006; 80(3): 1376 - 1384. [Abstract] [Full Text] [PDF]

				M. Schumann and M. Dobbelstein Adenovirus-Induced Extracellular Signal-Regulated Kinase Phosphorylation during the Late Phase of Infection Enhances Viral Protein Levels and Virus Progeny Cancer Res., February 1, 2006; 66(3): 1282 - 1288. [Abstract] [Full Text] [PDF]

				Y. Wang, S.-A. Xue, G. Hallden, J. Francis, M. Yuan, B. E. Griffin, and N. R. Lemoine Virus-Associated RNA I-Deleted Adenovirus, a Potential Oncolytic Agent Targeting EBV-Associated Tumors Cancer Res., February 15, 2005; 65(4): 1523 - 1531. [Abstract] [Full Text] [PDF]

				R. L. Chu, D. E. Post, F. R. Khuri, and E. G. Van Meir Use of Replicating Oncolytic Adenoviruses in Combination Therapy for Cancer Clin. Cancer Res., August 15, 2004; 10(16): 5299 - 5312. [Abstract] [Full Text] [PDF]