Carcinogenesis Advance Access originally published online on May 9, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis, Vol. 24, No. 7, 1225-1231,
July 2003
© 2003 Oxford University Press
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Mechanisms by which energy restriction inhibits rat mammary carcinogenesis: in vivo effects of corticosterone on cell cycle machinery in mammary carcinomas
Cancer Prevention Laboratory, Colorado State University, Fort Collins, 111 Shepardson, 1173 Campus Delivery, Fort Collins, CO 80523-1173, USA
1 To whom correspondence should be addressed Email: henry.thompson{at}colostate.edu
Increased secretion of adrenal cortical steroids may account in part for its cancer inhibitory activity of energy restriction (ER). To test this hypothesis, a study was conducted to determine the effects of dietary administration of corticosterone on the post-initiation stage of mammary carcinogenesis. Eighty-four female Sprague–Dawley rats were injected with 50 mg 1-methyl-1-nitrosourea/kg body wt (i.p.) at 21 days of age. One week later, animals were randomly divided into three groups and fed control diet, or that diet to which was added 200 or 400 mg corticosterone/kg. Diets were fed for 5 weeks after which the experiment was terminated. With increasing dietary corticosterone, a dose-dependent reduction in the incidence (P = 0.03), multiplicity (P = 0.003) and size (P < 0.003) of mammary carcinomas was observed. Dietary administration of corticosterone also reduced plasma insulin-like growth factor-1 (IGF-1) and levels of IGF-1 receptor in mammary carcinomas (P < 0.01). In order to investigate molecular mechanisms underlying anticancer activity, the levels and activities of cell cycle components involved in the G1–S transition were investigated in mammary carcinomas that emerged in treated animals. Levels of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)-2 and CDK-4 were reduced in carcinomas from corticosterone treated rats; whereas, levels of cyclin-dependent kinase inhibitors (CKI) Kip1/p27 and Cip1/p21 were elevated. Binding of these CKIs to both the cyclin D1–CDK-4 complex and the cyclin E–CDK-2 complex were increased and the kinase activities of these complexes were reduced with increasing dietary corticosterone. These effects were consistent with those observed in response to ER in vivo and corticosterone exposure in vitro. Whereas the effects of exogenously administered corticosterone and ER had many similarities, the lower efficacy of corticosterone versus ER in inhibiting the carcinogenic process imply that changes in cortical steroid metabolism alone are unlikely to explain the cancer inhibitory activity of ER.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Ogino, K. Shima, K. Nosho, N. Irahara, Y. Baba, B. M. Wolpin, E. L. Giovannucci, J. A. Meyerhardt, and C. S. Fuchs A Cohort Study of p27 Localization in Colon Cancer, Body Mass Index, and Patient Survival Cancer Epidemiol. Biomarkers Prev., June 1, 2009; 18(6): 1849 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Jiang, Z. Zhu, and H. J. Thompson Effects of Physical Activity and Restricted Energy Intake on Chemically Induced Mammary Carcinogenesis Cancer Prevention Research, April 1, 2009; 2(4): 338 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lu, L. Xie, J. Sylvester, J. Wang, J. Bai, R. Baybutt, and W. Wang Different Gene Expression of Skin Tissues Between Mice with Weight Controlled by Either Calorie Restriction or Physical Exercise Experimental Biology and Medicine, April 1, 2007; 232(4): 473 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Takayama, I. Rogatsky, L. E. Schwarcz, and B. D. Darimont The Glucocorticoid Receptor Represses Cyclin D1 by Targeting the Tcf-beta-Catenin Complex J. Biol. Chem., June 30, 2006; 281(26): 17856 - 17863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Stewart, K. Koehler, W. Jackson, J. Hawley, W. Wang, A. Au, R. Myers, and D. F. Birt Prevention of mouse skin tumor promotion by dietary energy restriction requires an intact adrenal gland and glucocorticoid supplementation restores inhibition Carcinogenesis, June 1, 2005; 26(6): 1077 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Abrous, M. Koehl, and M. Le Moal Adult Neurogenesis: From Precursors to Network and Physiology Physiol Rev, April 1, 2005; 85(2): 523 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Voskuil, A. Vrieling, L. J. van't Veer, E. Kampman, and M. A. Rookus The Insulin-like Growth Factor System in Cancer Prevention: Potential of Dietary Intervention Strategies Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 195 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Hilakivi-Clarke, C Wang, M Kalil, R Riggins, and R G Pestell Nutritional modulation of the cell cycle and breast cancer Endocr. Relat. Cancer, December 1, 2004; 11(4): 603 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Jiang, Z. Zhu, J. N. McGinley, and H. J. Thompson Adrenalectomy Does Not Block the Inhibition of Mammary Carcinogenesis by Dietary Energy Restriction in Rats J. Nutr., May 1, 2004; 134(5): 1152 - 1156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Cavigelli and M. K. McClintock Fear of novelty in infant rats predicts adult corticosterone dynamics and an early death PNAS, December 23, 2003; 100(26): 16131 - 16136. [Abstract] [Full Text] [PDF]
|
|