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
Services
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
Google Scholar
Right arrow Articles by Rathi, A. V.
Right arrow Articles by Pipas, J. M.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rathi, A. V.
Right arrow Articles by Pipas, J. M.

 Previous Article  |  Next Article 

Journal of Virology, September 2009, p. 9521-9531, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00583-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Simian Virus 40 T-Antigen-Mediated Gene Regulation in Enterocytes Is Controlled Primarily by the Rb-E2F Pathway{triangledown}

Abhilasha V. Rathi,1 M. Teresa Sáenz Robles,1 Paul G. Cantalupo,1 Robert H. Whitehead,2 and James M. Pipas1*

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260,1 Cellular and Animal Modeling Core, Vanderbilt Digestive Disease Research Center, Vanderbilt University, Nashville, Tennessee 372322

Received 20 March 2009/ Accepted 23 June 2009

Simian virus 40 large T antigen (TAg) contributes to cell transformation, in part, by targeting two well-characterized tumor suppressors, pRb and p53. TAg expression affects the transcriptional circuits controlled by Rb and by p53. We have performed a microarray analysis to examine the global change in gene expression induced by wild-type TAg (TAgwt) and TAg mutants, in an effort to link changes in gene expression to specific transforming functions. For this analysis we have used enterocytes from the mouse small intestine expressing TAg. Expression of TAgwt in the mouse intestine results in hyperplasia and dysplasia. Our analysis indicates that practically all gene expression regulated by TAg in enterocytes is dependent upon its binding and inactivation of the Rb family proteins. To further dissect the role of the Rb family in the induction of intestinal hyperplasia, we have screened several lines of transgenic mice expressing a truncated TAg (TAgN136), which is able to interfere with the Rb pathway but lacks the functions associated with the carboxy terminus of the protein. This analysis confirmed the pivotal association between the Rb pathway and the induction of intestinal hyperplasia and revealed that upregulation of p53 target genes is not associated with the tumorigenic phenotype. Furthermore, we found that TAgN136 was sufficient to induce intestinal hyperplasia, although the appearance of dysplasia was significantly delayed.

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

{triangledown} Published ahead of print on 1 July 2009.

Journal of Virology, September 2009, p. 9521-9531, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00583-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»