Carcinogenesis Advance Access originally published online on April 8, 2004
Carcinogenesis 2004 25(9):1747-1755; doi:10.1093/carcin/bgh160
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis vol.25 no.9 © Oxford University Press 2004; all rights reserved.
ARTICLE |
PPAR
influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis
1 Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, 2 Veterinary and Tumor Pathology Section, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702 and 3 Department of Veterinary Science and Center for Molecular Toxicology, The Pennsylvania State University, University Park, PA 16802, USA
4 Present address: Department of Life Sciences, Mokwon University, Taejon 302-729, Korea
5 To whom correspondence should be addressed Email: fjgonz{at}helix.nih.gov
Peroxisome proliferator-activated receptor 
(PPAR), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPAR ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPAR in mammary carcinogenesis, PPAR wild-type (+/+) or heterozygous (+/–) mice were administered 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPAR(+/+) littermate controls, PPAR(+/–) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPAR(+/–) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPAR(+/–) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPAR haploinsufficiency to DMBA-mediated carcinogenesis and suggest that PPAR may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPAR-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Yin, H. Yuan, X. Zeng, L. Kopelovich, and R. I. Glazer Inhibition of Peroxisome Proliferator-Activated Receptor {gamma} Increases Estrogen Receptor-Dependent Tumor Specification Cancer Res., January 15, 2009; 69(2): 687 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Conzen Minireview: Nuclear Receptors and Breast Cancer Mol. Endocrinol., October 1, 2008; 22(10): 2215 - 2228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schmuth, Y. J. Jiang, S. Dubrac, P. M. Elias, and K. R. Feingold Thematic Review Series: Skin Lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology J. Lipid Res., March 1, 2008; 49(3): 499 - 509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Guo, R. P. Chi, D. M. Hernandez, W. Auttachoat, and J. F. Zheng Decreased 7,12-dimethylbenz[a]anthracene-induced carcinogenesis coincides with the induction of antitumor immunities in adult female B6C3F1 mice pretreated with genistein Carcinogenesis, December 1, 2007; 28(12): 2560 - 2566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chandramouli, J. Shi, Y. Feng, H. Holubec, R. M.Shanas, A. K. Bhattacharyya, W. Zheng, and M. A. Nelson Haploinsufficiency of the cdc2l gene contributes to skin cancer development in mice Carcinogenesis, September 1, 2007; 28(9): 2028 - 2035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Yee, N. Williams, P. Wen, D. C. Young, J. Lester, M. V. Johnson, W. B. Farrar, M. J. Walker, S. P. Povoski, S. Suster, et al. Pilot Study of Rosiglitazone Therapy in Women with Breast Cancer: Effects of Short-term Therapy on Tumor Tissue and Serum Markers Clin. Cancer Res., January 1, 2007; 13(1): 246 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Yang, R. Kurotani, A. Yamada, S. Kimura, and F. J. Gonzalez Peroxisome Proliferator-Activated Receptor {alpha} Activation during Pregnancy Severely Impairs Mammary Lobuloalveolar Development in Mice Endocrinology, October 1, 2006; 147(10): 4772 - 4780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lei, M. Abdelrahim, and S. Safe 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit ovarian cancer cell growth through peroxisome proliferator-activated receptor-dependent and independent pathways. Mol. Cancer Ther., September 1, 2006; 5(9): 2324 - 2336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Adachi, R Kurotani, K Morimura, Y Shah, M Sanford, B B Madison, D L Gumucio, H E Marin, J M Peters, H A Young, et al. Peroxisome proliferator activated receptor {gamma} in colonic epithelial cells protects against experimental inflammatory bowel disease Gut, August 1, 2006; 55(8): 1104 - 1113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Peraza, A. D. Burdick, H. E. Marin, F. J. Gonzalez, and J. M. Peters The Toxicology of Ligands for Peroxisome Proliferator-Activated Receptors (PPAR) Toxicol. Sci., April 1, 2006; 90(2): 269 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lu, K. Imamura, S. Nomura, K.-i. Mafune, A. Nakajima, T. Kadowaki, N. Kubota, Y. Terauchi, G. Ishii, A. Ochiai, et al. Chemopreventive Effect of Peroxisome Proliferator-Activated Receptor {gamma} on Gastric Carcinogenesis in Mice Cancer Res., June 1, 2005; 65(11): 4769 - 4774. [Abstract] [Full Text] [PDF]
|
|