Estrogen deprivation and excess energy supply accelerate 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth in C3H/HeN mice.
- Author:
Jin KIM
1
;
Yoon Hee LEE
;
Jung Han Yoon PARK
;
Mi Kyung SUNG
Author Information
- Publication Type:Original Article
- Keywords: Breast cancer; obesity; estrogen; postmenopause
- MeSH: Animals; Breast Neoplasms; Cellular Microenvironment; Diet; Diet, High-Fat; Estrogens*; Fatty Acids, Nonesterified; Female; Humans; Insulin; Lipid Metabolism; Liver; Mice*; Obesity; Postmenopause; Receptor, Insulin; Risk Factors; RNA, Messenger; TOR Serine-Threonine Kinases; Tumor Burden
- From:Nutrition Research and Practice 2015;9(6):628-636
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/OBJECTIVES: Obesity is a risk factor of breast cancer in postmenopausal women. Estrogen deprivation has been suggested to cause alteration of lipid metabolism thereby creating a cellular microenvironment favoring tumor growth. The aim of this study is to investigate the effects of estrogen depletion in combination with excess energy supply on breast tumor development. MATERIALS/METHODS: Ovariectomized (OVX) or sham-operated C3H/HeN mice at 4 wks were provided with either a normal diet or a high-fat diet (HD) for 16 weeks. Breast tumors were induced by administration of 7,12-dimethylbenz(a)anthracene once a week for six consecutive weeks. RESULTS: Study results showed higher serum concentrations of free fatty acids and insulin in the OVX+HD group compared to other groups. The average tumor volume was significantly larger in OVX+HD animals than in other groups. Expressions of mammary tumor insulin receptor and mammalian target of rapamycin proteins as well as the ratio of pAKT/AKT were significantly increased, while pAMPK/AMPK was decreased in OVX+HD animals compared to the sham-operated groups. Higher relative expression of liver fatty acid synthase mRNA was observed in OVX+HD mice compared with other groups. CONCLUSIONS: These results suggest that excess energy supply affects the accelerated mammary tumor growth in estrogen deprived mice.