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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by van der Weyden, L.
Right arrow Articles by Bradley, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van der Weyden, L.
Right arrow Articles by Bradley, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2005, p. 8356-8367, Vol. 25, No. 18
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.18.8356-8367.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The RASSF1A Isoform of RASSF1 Promotes Microtubule Stability and Suppresses Tumorigenesis

L. van der Weyden,1 K. K. Tachibana,2,{dagger} M. A. Gonzalez,2,{dagger} D. J. Adams,1,{dagger} B. L. Ng,1 R. Petty,1 A. R. Venkitaraman,2 M. J. Arends,3 and A. Bradley1*

Mouse Genomics Lab, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom,1 MRC Cancer Cell Unit, Hutchinson/MRC Research Centre, Hills Road, Cambridge, United Kingdom,2 Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom3

Received 10 February 2005/ Returned for modification 23 March 2005/ Accepted 30 June 2005

The RASSF1A isoform of RASSF1 is frequently inactivated by epigenetic alterations in human cancers, but it remains unclear if and how it acts as a tumor suppressor. RASSF1A overexpression reduces in vitro colony formation and the tumorigenicity of cancer cell lines in vivo. Conversely, RASSF1A knockdown causes multiple mitotic defects that may promote genomic instability. Here, we have used a genetic approach to address the function of RASSF1A as a tumor suppressor in vivo by targeted deletion of Rassf1A in the mouse. Rassf1A null mice were viable and fertile and displayed no pathological abnormalities. Rassf1A null embryonic fibroblasts displayed an increased sensitivity to microtubule depolymerizing agents. No overtly altered cell cycle parameters or aberrations in centrosome number were detected in Rassf1A null fibroblasts. Rassf1A null fibroblasts did not show increased sensitivity to microtubule poisons or DNA-damaging agents and showed no evidence of gross genomic instability, suggesting that cellular responses to genotoxins were unaffected. Rassf1A null mice showed an increased incidence of spontaneous tumorigenesis and decreased survival rate compared with wild-type mice. Irradiated Rassf1A null mice also showed increased tumor susceptibility, particularly to tumors associated with the gastrointestinal tract, compared with wild-type mice. Thus, our results demonstrate that Rassf1A acts as a tumor suppressor gene.

* Corresponding author. Mailing address: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom. Phone: 44-(0)1223-834-244. Fax: 44-(0)1223-494-714. E-mail: abradley{at}sanger.ac.uk.

{dagger} These authors contributed equally.

Molecular and Cellular Biology, September 2005, p. 8356-8367, Vol. 25, No. 18
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.18.8356-8367.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Avruch, J., Xavier, R., Bardeesy, N., Zhang, X.-f., Praskova, M., Zhou, D., Xia, F. (2009). Rassf Family of Tumor Suppressor Polypeptides. J. Biol. Chem. 284: 11001-11005 [Abstract] [Full Text]  
  • Song, S. J., Song, M. S., Kim, S. J., Kim, S. Y., Kwon, S. H., Kim, J. G., Calvisi, D. F., Kang, D., Lim, D.-S. (2009). Aurora A Regulates Prometaphase Progression by Inhibiting the Ability of RASSF1A to Suppress APC-Cdc20 Activity. Cancer Res. 69: 2314-2323 [Abstract] [Full Text]  
  • Foley, C. J., Freedman, H., Choo, S. L., Onyskiw, C., Fu, N. Y., Yu, V. C., Tuszynski, J., Pratt, J. C., Baksh, S. (2008). Dynamics of RASSF1A/MOAP-1 Association with Death Receptors. Mol. Cell. Biol. 28: 4520-4535 [Abstract] [Full Text]  
  • Donninger, H., Vos, M. D., Clark, G. J. (2007). The RASSF1A tumor suppressor. J. Cell Sci. 120: 3163-3172 [Abstract] [Full Text]  
  • Estrabaud, E., Lassot, I., Blot, G., Le Rouzic, E., Tanchou, V., Quemeneur, E., Daviet, L., Margottin-Goguet, F., Benarous, R. (2007). RASSF1C, an Isoform of the Tumor Suppressor RASSF1A, Promotes the Accumulation of {beta}-Catenin by Interacting with {beta}TrCP. Cancer Res. 67: 1054-1061 [Abstract] [Full Text]  
  • Dallol, A., Cooper, W. N., Al-Mulla, F., Agathanggelou, A., Maher, E. R., Latif, F. (2007). Depletion of the Ras Association Domain Family 1, Isoform A-Associated Novel Microtubule-Associated Protein, C19ORF5/MAP1S, Causes Mitotic Abnormalities. Cancer Res. 67: 492-500 [Abstract] [Full Text]  
  • Lee, H., Lee, D. J., Oh, S. P., Park, H. D., Nam, H. H., Kim, J. M., Lim, D.-S. (2006). Mouse emi1 Has an Essential Function in Mitotic Progression during Early Embryogenesis.. Mol. Cell. Biol. 26: 5373-5381 [Abstract] [Full Text]  
  • Oh, H. J., Lee, K.-K., Song, S. J., Jin, M. S., Song, M. S., Lee, J. H., Im, C. R., Lee, J.-O., Yonehara, S., Lim, D.-S. (2006). Role of the Tumor Suppressor RASSF1A in Mst1-Mediated Apoptosis.. Cancer Res. 66: 2562-2569 [Abstract] [Full Text]  


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