Abstract

Many attempts have been made to identify dietary components that prevent development of breast cancer and/or mammary tumors (MTs). Few studies have produced conclusive findings. However, chronic caloric restriction consistently lowers MT incidence and extends latency in rodents. We find that intermittent restriction/refeeding prevents MT development in transgenic MMTV-TGF-a mice to a greater degree than does chronic restriction, i.e., 3% vs 44% incidence (vs 77% for ad libitum-fed mice). Thus, the manner in which calories are restricted has a major impact on MT development. Hypotheses: 1- The protective effect of intermittent restriction/refeeding is mediated by decreased serum IGF-I and leptin and effects on signaling pathways and/or proliferation/apoptosis; 2-The protective effect of intermittent restriction/refeeding is dependent upon periods of moderately severe caloric restriction and is modified by caloric intake and/or nutrient composition during refeeding; 3- The protective effects of chronic restriction and intermittent restriction/refeeding are dependent upon tumor etiology.
In Specific Aim 1 the effect of intermittent restriction/refeeding and chronic restriction on serum IGF-I and leptin in longitudinal and cross-sectional protocols will be assessed.
In Specific Aim 2 the effect of intermittent restriction/refeeding and chronic restriction on apoptosis, proliferation, and gene expression of IGF-I and leptin and their receptors in mammary tissue and MTs will be determined.
In Specific Aim 3 the effect of serum leptin levels on the protective response of intermittent restriction/refeeding regimen on MT development will be determined.
Specific Aim 4 will determine if the protective effect of intermittent caloric restriction/refeeding is dependent upon the MT oncogene and/or background strain of the transgenic mouse. Our long-term objectives are to establish nutrition intervention strategies applicable to humans and/or to provide insights leading to the development of chemopreventive agents to mimic this protective effect. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA101858-05
Application #
7368099
Study Section
Special Emphasis Panel (ZRG1-CDP (01))
Program Officer
Ross, Sharon A
Project Start
2004-04-01
Project End
2010-02-28
Budget Start
2008-03-01
Budget End
2010-02-28
Support Year
5
Fiscal Year
2008
Total Cost
$233,253
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
Organized Research Units
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Dogan, Soner; Ray, Amitabha; Cleary, Margot P (2017) The influence of different calorie restriction protocols on serum pro-inflammatory cytokines, adipokines and IGF-I levels in female C57BL6 mice: short term and long term diet effects. Meta Gene 12:22-32
Mizuno, Nancy K; Rogozina, Olga P; Seppanen, Christine M et al. (2013) Combination of intermittent calorie restriction and eicosapentaenoic acid for inhibition of mammary tumors. Cancer Prev Res (Phila) 6:540-7
Rogozina, Olga P; Nkhata, Katai J; Nagle, Emily J et al. (2013) The protective effect of intermittent calorie restriction on mammary tumorigenesis is not compromised by consumption of a high fat diet during refeeding. Breast Cancer Res Treat 138:395-406
Grossmann, Michael E; Cleary, Margot P (2012) The balance between leptin and adiponectin in the control of carcinogenesis - focus on mammary tumorigenesis. Biochimie 94:2164-71
Dogan, Soner; Johannsen, Anna C; Grande, Joseph P et al. (2011) Effects of intermittent and chronic calorie restriction on mammalian target of rapamycin (mTOR) and IGF-I signaling pathways in mammary fat pad tissues and mammary tumors. Nutr Cancer 63:389-401
Rogozina, Olga P; Bonorden, Melissa J L; Seppanen, Christine N et al. (2011) Effect of chronic and intermittent calorie restriction on serum adiponectin and leptin and mammary tumorigenesis. Cancer Prev Res (Phila) 4:568-81
Grossmann, Michael E; Ray, Amitabha; Nkhata, Katai J et al. (2010) Obesity and breast cancer: status of leptin and adiponectin in pathological processes. Cancer Metastasis Rev 29:641-53
Rogozina, Olga P; Bonorden, Melissa J L; Grande, Joseph P et al. (2009) Serum insulin-like growth factor-I and mammary tumor development in ad libitum-fed, chronic calorie-restricted, and intermittent calorie-restricted MMTV-TGF-alpha mice. Cancer Prev Res (Phila Pa) 2:712-9
Saykally, Jessica N; Dogan, Soner; Cleary, Margot P et al. (2009) The ZEB1 transcription factor is a novel repressor of adiposity in female mice. PLoS One 4:e8460
Cleary, Margot P; Hu, Xin; Grossmann, Michael E et al. (2007) Prevention of mammary tumorigenesis by intermittent caloric restriction: does caloric intake during refeeding modulate the response? Exp Biol Med (Maywood) 232:70-80

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