This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Markovics, J. A.
Right arrow Articles by Pipas, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Markovics, J. A.
Right arrow Articles by Pipas, J. M.

 Previous Article  |  Next Article 

Journal of Virology, June 2005, p. 7492-7502, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7492-7502.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Intestinal Dysplasia Induced by Simian Virus 40 T Antigen Is Independent of p53

Jennifer A. Markovics,1 Patrick A. Carroll,1 M. Teresa Sáenz Robles,1 Hannah Pope,1 Craig M. Coopersmith,2 and James M. Pipas1*

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260,1 Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 631102

Received 3 November 2004/ Accepted 22 February 2005

Transgenic mice expressing simian virus 40 large T antigen in enterocytes develop intestinal hyperplasia that progresses to dysplasia with age. Hyperplasia is dependent on T antigen binding to the retinoblastoma (pRb) family of tumor suppressor proteins. Mice expressing a truncated T antigen that inactivates the pRb-family, but is defective for binding p53, exhibit hyperplasia but do not progress to dysplasia. We hypothesized that the inhibition of the pRb family leads to entry of enterocytes into the cell cycle, resulting in hyperplasia, while inactivation of p53 is required for progression to dysplasia. Therefore, we examined T antigen/p53 complexes from the intestines of transgenic mice. We found that T antigen did not induce p53 stabilization, and we could not detect T antigen/p53 complexes in villus enterocytes. In contrast, T antigen expression led to a large increase in the levels of the cyclin-dependent kinase inhibitor p21. Furthermore, mice in which pRb was inactivated by a truncated T antigen in a p53 null background exhibited intestinal hyperplasia but no progression to dysplasia. These data indicate that loss of p53 function does not play a role in T antigen-induced dysplasia in the intestine. Rather, some unknown function of T antigen is essential for progression beyond hyperplasia.

* Corresponding author. Mailing address: 559 Crawford Hall, Department of Biological Sciences, University of Pittsburgh, Pittsburgh PA 15260. Phone: (412) 624-4691. Fax: (412) 624-4759. E-mail: pipas{at}pitt.edu.

Journal of Virology, June 2005, p. 7492-7502, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7492-7502.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rathi, A. V., Saenz Robles, M. T., Cantalupo, P. G., Whitehead, R. H., Pipas, J. M. (2009). Simian Virus 40 T-Antigen-Mediated Gene Regulation in Enterocytes Is Controlled Primarily by the Rb-E2F Pathway. J. Virol. 83: 9521-9531 [Abstract] [Full Text]  
  • Saenz-Robles, M. T., Markovics, J. A., Chong, J.-L., Opavsky, R., Whitehead, R. H., Leone, G., Pipas, J. M. (2007). Intestinal Hyperplasia Induced by Simian Virus 40 Large Tumor Antigen Requires E2F2. J. Virol. 81: 13191-13199 [Abstract] [Full Text]  
  • Rathi, A. V., Saenz Robles, M. T., Pipas, J. M. (2007). Enterocyte Proliferation and Intestinal Hyperplasia Induced by Simian Virus 40 T Antigen Require a Functional J Domain. J. Virol. 81: 9481-9489 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»