This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 Google Scholar
Google Scholar
Right arrow Articles by Ursini-Siegel, J.
Right arrow Articles by Muller, W. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ursini-Siegel, J.
Right arrow Articles by Muller, W. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2007, p. 6361-6371, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00686-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Elevated Expression of DecR1 Impairs ErbB2/Neu-Induced Mammary Tumor Development{triangledown} ,{dagger}

Josie Ursini-Siegel,1 Ashish B. Rajput,2 Huiling Lu,3 Virginie Sanguin-Gendreau,1 Dongmei Zuo,1 Vasilios Papavasiliou,1 Cynthia Lavoie,1 Jason Turpin,1 Katherine Cianflone,3 David G. Huntsman,2 and William J. Muller1*

Departments of Medicine and Biochemistry, McGill University, Montreal, Quebec, Canada H3A 1A1,1 Genetic Pathology Evaluation Centre, Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada V6H 3Z6,2 Department of Physiology and Anatomy, Centre de Recherche Hopital Laval, Universite Laval, Quebec, Canada G1V 3N53

Received 19 April 2007/ Returned for modification 29 May 2007/ Accepted 29 June 2007

Tumor cells utilize glucose as a primary energy source and require ongoing lipid biosynthesis for growth. Expression of DecR1, an auxiliary enzyme in the fatty acid ß-oxidation pathway, is significantly diminished in numerous spontaneous mammary tumor models and in primary human breast cancer. Moreover, ectopic expression of DecR1 in ErbB2/Neu-induced mammary tumor cells is sufficient to reduce levels of ErbB2/Neu expression and impair mammary tumor outgrowth. This correlates with a decreased proliferative index and reduced rates of de novo fatty acid synthesis in DecR1-expressing breast cancer cells. Although DecR1 expression does not affect glucose uptake in ErbB2/Neu-transformed cells, sustained expression of DecR1 protects mammary tumor cells from apoptotic cell death following glucose withdrawal. Moreover, expression of catalytically impaired DecR1 mutants in Neu-transformed breast cancer cells restored Neu expression levels and increased mammary tumorigenesis in vivo. These results argue that DecR1 is sufficient to limit breast cancer cell proliferation through its ability to limit the extent of oncogene expression and reduce steady-state levels of de novo fatty acid synthesis. Furthermore, DecR1-mediated suppression of tumorigenesis can be uncoupled from its effects on Neu expression. Thus, while downregulation of Neu expression may contribute to DecR1-mediated tumor suppression in certain cell types, this is not an obligate event in all Neu-transformed breast cancer cells.

* Corresponding author. Mailing address: Departments of Medicine and Biochemistry, McGill University, Montreal, Quebec, Canada H3A 1A1. Phone: (514) 934-1934, ext. 36383. Fax: (514) 843-1478. E-mail: william.muller{at}mcgill.ca

{triangledown} Published ahead of print on 16 July 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, September 2007, p. 6361-6371, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00686-07
Copyright © 2007, 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»