Carcinogenesis Advance Access published online on January 9, 2006
Carcinogenesis, doi:10.1093/carcin/bgi335
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Gastroenterology & Liver Research Center, Brown Medical School and Rhode Island Hospital, Providence, Rhode Island
* To whom correspondence should be addressed. Oxidative stress has a complex effect on cancer development. To further study this process, we induced colon tumors with azoxymethane (AOM) in mice deficient for uncoupling protein-2 (UCP2). UCP2 has recently emerged as a negative regulator of mitochondrial oxidant production. When overexpressed, UCP2 protects cells from oxidative stress, while its absence may cause abundance of reactive oxygen species, release of pro-inflammatory cytokines, and persistent activation of NF-
Received October 24, 2005
Revised December 2, 2005
Accepted January 3, 2006
CANCER BIOLOGY
Enhanced colon tumor induction in uncoupling protein-2 deficient mice is associated with NF-
Zoltán Derdák 1,
Péter Fülöp 2,
Edmond Sabo 3,
Rose Tavares 3,
Eric P. Berthiaume 1,
Murray B. Resnick 3,
György Paragh 4,
Jack R. Wands 1,
and
György Baffy 1 *
B activation and oxidative stress
2 Division of Gastroenterology & Liver Research Center, Brown Medical School and Rhode Island Hospital, Providence, Rhode Island; First Department of Medicine, University of Debrecen Medical and Health Science Center, Debrecen, Hungary
3 Department of Pathology, Brown Medical School and Rhode Island Hospital, Providence, Rhode Island
4 First Department of Medicine, University of Debrecen Medical and Health Science Center, Debrecen, Hungary
György Baffy, E-mail: gbaffy{at}brown.edu
Abstract 
B, a pleiotropic transcription factor with an increasingly recognized role in cancer. Here we show that Ucp2-/- mice develop more aberrant crypt foci and colon tumors than Ucp2+/+ littermates when examined 24 weeks after the completion of treatment with AOM (10 mg/kg i.p. weekly for a total of 6 weeks, n = 8 to 12). This effect is primarily seen in the proximal colon of Ucp2-/- mice (P < 0.05), in association with changes indicative of increased oxidative stress (increased staining for malondialdehyde and inducible nitric oxide synthase), enhanced NF-B activation (increased levels of phosphorylated IB and increased nuclear presence of p65), and a disrupted balance between intestinal epithelial cell proliferation (greater BrdU incorporation rates and increased phosphorylation of ERK1/2 and AKT) and apoptosis (decreased number of terminal deoxynucleotidyltransferase-mediated nick end labeling (TUNEL)-positive cells and increased expression of Bcl-2). In conclusion, our findings provide the first in vivo evidence for a link between UCP2 and tumorigenesis and indicate the need for additional studies to assess the role mitochondrial uncoupling in cancer development.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Pi, Y. Bai, K. W. Daniel, D. Liu, O. Lyght, D. Edelstein, M. Brownlee, B. E. Corkey, and S. Collins Persistent Oxidative Stress Due to Absence of Uncoupling Protein 2 Associated with Impaired Pancreatic {beta}-Cell Function Endocrinology, July 1, 2009; 150(7): 3040 - 3048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Dai, L. Qiao, K. W. Chan, M. Yang, J. Ye, J. Ma, B. Zou, Q. Gu, J. Wang, R. Pang, et al. Peroxisome Proliferator-Activated Receptor-{gamma} Contributes to the Inhibitory Effects of Embelin on Colon Carcinogenesis Cancer Res., June 1, 2009; 69(11): 4776 - 4783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Pecqueur, T. Bui, C. Gelly, J. Hauchard, C. Barbot, F. Bouillaud, D. Ricquier, B. Miroux, and C. B. Thompson Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization FASEB J, January 1, 2008; 22(1): 9 - 18. [Abstract] [Full Text] [PDF]
|
|