Molecular Biology of the Cell track citations

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print May 25, 2005
Mol. Biol. Cell 10.1091/mbc.E04-12-1104

A more recent version of this article appeared on August 1, 2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E04-12-1104v1
16/8/3832    most recent
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vultur, A.
Right arrow Articles by Raptis, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vultur, A.
Right arrow Articles by Raptis, L.

Submitted on December 22, 2004
Revised on April 18, 2005
Accepted on May 18, 2005

Stat3 Is Required for Full Neoplastic Transformation by the Simian Virus 40 Large Tumor Antigen

Adina Vultur,* Rozanne Arulanandam,* James Turkson,{dagger} Guilian Niu,{dagger} Richard Jove,{dagger} and Leda Raptis*

*Departments of Microbiology and Immunology and Pathology, Queen’s University, Kingston, Ontario K7L 3N6, Canada; {dagger}H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612

Monitoring Editor: Gerard Evan

To investigate the role of Stat3 (signal transducer and activator of transcription-3) in neoplastic transformation by the Large Tumor antigen of Simian Virus 40 (TAg), murine fibroblasts were rendered deficient in Stat3 activity through expression of a Stat3-specific siRNA or a Cre-loxP recombination system. The results demonstrate that growth rate, formation of foci overgrowing a monolayer of normal cells and colony formation in soft agar were dramatically reduced in Stat3-deficient cells. In addition, TAg expression led to increased Stat3 tyrosine phosphorylation, DNA binding and transcriptional activity, suggesting that Stat3 is required for TAg-mediated neoplasia. Stat3 activation was prevented by blocking the binding of TAg to pRb (retinoblastoma-susceptibility gene product), while genetic ablation of pRb increased Stat3 activity, suggesting that pRb inactivation by TAg might be responsible for the observed Stat3 activation. Stat3 activation by TAg was suppressed following inhibition of c-Src, JAKs or the insulin-like growth factor receptor. On the other hand, targeted disruption of the Fer kinase or pharmacological inhibition of Abl had no effect. Inhibition of Src activity led to Stat3 down-regulation as well as apoptosis of sparsely growing, TAg-transformed cells. However, Src inhibition was relatively ineffective in confluent cells, consistent with previous results indicating that cell to cell adhesion activates Stat3 by a Src-independent mechanism. Direct Stat3 inhibition on the other hand induced apoptosis very effectively in confluent cells, which could have significant therapeutic implications. Taken together, our results suggest that Stat3 is an important component of a pathway emanating from TAg and leading to neoplastic conversion.

Address correspondence to: Leda Raptis (raptisl{at}post.queensu.ca)




This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
A. Vultur, R. Buettner, C. Kowolik, W. Liang, D. Smith, F. Boschelli, and R. Jove
SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells
Mol. Cancer Ther., May 1, 2008; 7(5): 1185 - 1194.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
C. Guo, G. Wu, J. L. Chin, G. Bauman, M. Moussa, F. Wang, N. M. Greenberg, S. S. Taylor, and J. W. Xuan
Bub1 Up-Regulation and Hyperphosphorylation Promote Malignant Transformation in SV40 Tag-Induced Transgenic Mouse Models
Mol. Cancer Res., December 1, 2006; 4(12): 957 - 969.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2005 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.