Estrogen deprivation and excess energy supply accelerate 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth in C3H/HeN mice
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (65)
- Grossmann ME, "Obesity and breast cancer: status of leptin and adiponectin in pathological processes", Cancer Metastasis Rev, 29, pp.641~653 (2010)
- Rohan TE, "Body fat and breast cancer risk in postmenopausal women: a longitudinal study", J Cancer Epidemiol, 2013, pp.754815~ (2013)
- Calle EE, "Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults", N Engl J Med, 348, pp.1625~1638 (2003)
- Eliassen AH, "Adult weight change and risk of postmenopausal breast cancer", JAMA, 296, pp.193~201 (2006)
- World Cancer Research Fund (GB), "Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective" (2007), American Institute for Cancer Research
- World Cancer Research Fund International, Continuous Update Project (GB), "Diet, Nutrition, Physical Activity, and the Breast Cancer Survivors" (2014), World Cancer Research Fund International
- Brennan SF, "Dietary fat and breast cancer mortality: a systematic review and meta-analysis", Crit Rev Food Sci Nutr (2015)
- Mourouti N, "Diet and breast cancer: a systematic review", Int J Food Sci Nutr, 66, pp.1~42 (2015)
- Demir B, "The effects of estrogen therapy and estrogen combined with different androgenic progestins on carbohydrate and lipid metabolism in overweight-obese younger postmenopausal women", Gynecol Endocrinol, 24, pp.347~353 (2008)
- Jensen LB, "Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study", J Bone Miner Res, 18, pp.333~342 (2003)
- Cooke PS, "Role of estrogens in adipocyte development and function", Exp Biol Med (Maywood), 229, pp.1127~1135 (2004)
- D'Eon TM, "Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways", J Biol Chem, 280, pp.35983~35991 (2005)
- Field FJ, "Polyunsaturated fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 cells: effect on fatty acid synthesis and triacylglycerol transport", Biochem J, 368, pp.855~864 (2002)
- Horton JD, "Sterol regulatory element-binding proteins: transcriptional activators of lipid synthesis", Biochem Soc Trans, 30, pp.1091~1095 (2002)
- Kuhl J, "Characterisation of subjects with early abnormalities of glucose tolerance in the Stockholm Diabetes Prevention Programme: the impact of sex and type 2 diabetes heredity", Diabetologia, 48, pp.35~40 (2005)
- Macotela Y, "Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism", Diabetes, 58, pp.803~812 (2009)
- Saengsirisuwan V, "Modulation of insulin resistance in ovariectomized rats by endurance exercise training and estrogen replacement", Metabolism, 58, pp.38~47 (2009)
- Gao H, "Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob", ob mice: a possible mechanism is through direct regulation of signal transducer and activator of transcription 3, 2006, pp.20, 1287~1299
- Vona-Davis L, "Adiposity, type 2diabetes and the metabolic syndrome in breast cancer", Obes Rev, 8, pp.395~408 (2007)
- Jouyandeh Z, "Metabolic syndrome and menopause", J Diabetes Metab Disord, 12, pp.1~ (2013)
- Frasca F, "The role of insulin receptors and IGF-I receptors in cancer and other diseases", Arch Physiol Biochem, 114, pp.23~37 (2008)
- Kim HJ, "Effects and prooxidant mechanisms of oxidized alpha-tocopherol on the oxidative stability of soybean oil", J Food Sci, 72, pp.C223~C230 (2007)
- Hong J, "Estrogen inhibits the effects of obesity and alcohol on mammary tumors and fatty liver", Int J Oncol, 39, pp.1443~1453 (2011)
- Blume-Jensen P, "Oncogenic kinase signalling", Nature, 411, pp.355~365 (2001)
- Reeves PG, "AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet", J Nutr, 123, pp.1939~1951 (1993)
- Park SY, "Effects of diet-induced obesity on colitis-associated colon tumor formation in A", J mice, 2012, pp.36, 273~280
- Stephenson GD, "Breast cancer and obesity: an update", Nutr Cancer, 45, pp.1~16 (2003)
- Healy LA, "Metabolic syndrome, central obesity and insulin resistance are associated with adverse pathological features in postmenopausal breast cancer", Clin Oncol (R Coll Radiol), 22, pp.281~288 (2010)
- Nadal A, "The role of oestrogens in the adaptation of islets to insulin resistance", J Physiol, 587, pp.5031~5037 (2009)
- Hong J, "Differential susceptibility to obesity between male, female and ovariectomized female mice", Nutr J, 8, pp.11~ (2009)
- Hakkak R, "Obesity increases the incidence of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in an ovariectomized Zucker rat model", Int J Oncol, 30, pp.557~563 (2007)
- Sylvester PW, "Effects of high dietary fat on the growth and development of ovarian-independent carcinogen-induced mammary tumors in rats", Cancer Res, 46, pp.763~769 (1986)
- Costa I, "Histopathologic characterization of mammary neoplastic lesions induced with 7,12 dimethylbenz (alpha)anthracene in the rat: a comparative analysis with human breast tumors", Arch Pathol Lab Med, 126, pp.915~927 (2002)
- Hwang IK, "Strain-specific differences in cell proliferation and differentiation in the dentate gyrus of C57BL", 6N and C3H, Brain Res, pp.2008, 1241[DOI]
- Suganami T, "Attenuation of obesity-induced adipose tissue inflammation in C3H", HeJ mice carrying a Toll-like receptor 4 mutation, 2007, pp.354, 45~49
- Lim DW, "Preventive effects of Citrus unshiu peel extracts on bone and lipid metabolism in OVX rats", Molecules, 19, pp.783~794 (2014)
- Choi JS, "Genistein reduced insulin resistance index through modulating lipid metabolism in ovariectomized rats", Nutr Res, 32, pp.844~855 (2012)
- Lane HW, "The effect of diet, exercise and 7,12-dimethylbenz(a)anthracene on food intake, body composition and carcass energy levels in virgin female BALB", c mice, 1991, pp.121, 1876~1882
- Ojeswi BK, "Protective effect of Thuja occidentalis against DMBA-induced breast cancer with reference to oxidative stress", Hum Exp Toxicol, 29, pp.369~375 (2010)
- Gambacciani M, "Body weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women", J Clin Endocrinol Metab, 82, pp.414~417 (1997)
- Asp ML, "Evidence for the contribution of insulin resistance to the development of cachexia in tumor-bearing mice", Int J Cancer, 126, pp.756~763 (2010)
- Suba Z, "Circulatory estrogen level protects against breast cancer in obese women", Recent Pat Anticancer Drug Discov, 8, pp.154~167 (2013)
- Koricanac G, "Insulin signaling in the liver and uterus of ovariectomized rats treated with estradiol", J Steroid Biochem Mol Biol, 108, pp.109~116 (2008)
- Swislocki A, "Effects of ovariectomy on indices of insulin resistance, hypertension, and cardiac energy metabolism in middle-aged spontaneously hypertensive rats (SHR)", Horm Metab Res, 34, pp.516~522 (2002)
- Carr MC, "The emergence of the metabolic syndrome with menopause", J Clin Endocrinol Metab, 88, pp.2404~2411 (2003)
- Pfeilschifter J, "Changes in proinflammatory cytokine activity after menopause", Endocr Rev, 23, pp.90~119 (2002)
- Gu JW, "Postmenopausal obesity promotes tumor angiogenesis and breast cancer progression in mice", Cancer Biol Ther, 11, pp.910~917 (2011)
- Nunez NP, "Obesity accelerates mouse mammary tumor growth in the absence of ovarian hormones", Nutr Cancer, 60, pp.534~541 (2008)
- Asselin J, "Effects of estradiol and prolactin on steroid receptor levels in 7,12-dimethylbenz(a)anthracene-induced mammary tumors and uterus in the rat", J Steroid Biochem, 9, pp.1079~1082 (1978)
- Sasaki GH, "On the mechanism of hormone action in 7,12dimethylbenz(a)anthracene-induced mammary tumor. I. Prolactin and progesterone effects on estrogen receptor in vitro", Cancer, 35, pp.645~651 (1975)
- Dao TL, "The role of ovarian hormones in initiating the induction of mammary cancer in rats by polynuclear hydrocarbons", Cancer Res, 22, pp.973~981 (1962)
- Rose DP, "Adverse effects of obesity on breast cancer prognosis, and the biological actions of leptin (review)", Int J Oncol, 21, pp.1285~1292 (2002)
- Daling JR, "Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma", Cancer, 92, pp.720~729 (2001)
- Belfiore A, "IGF and insulin receptor signaling in breast cancer", J Mammary Gland Biol Neoplasia, 13, pp.381~406 (2008)
- Wysocki PJ, "Obesity, hyperinsulinemia and breast cancer: novel targets and a novel role for metformin", Expert Rev Mol Diagn, 10, pp.509~519 (2010)
- Clark AS, "Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells", Mol Cancer Ther, 1, pp.707~717 (2002)
- Woo SL, "Metformin ameliorates hepatic steatosis and inflammation without altering adipose phenotype in diet-induced obesity", PLoS One, 9, pp.e91111~ (2014)
- Wohlers LM, "Changes in contraction-induced phosphorylation of AMPactivated protein kinase and mitogen-activated protein kinases in skeletal muscle after ovariectomy", J Cell Biochem, 107, pp.171~178 (2009)
- Tiainen M, "Growth arrest by the LKB1 tumor suppressor: induction of p21(WAF1", CIP1), 2002, pp.11, 1497~1504
- Jones RG, "AMP-activated protein kinase induces a p53-dependent metabolic checkpoint", Mol Cell, 18, pp.283~293 (2005)
- Chapuis N, "Perspectives on inhibiting mTOR as a future treatment strategy for hematological malignancies", Leukemia, 24, pp.1686~1699 (2010)
- Kim JY, "17beta-estradiol induces an interaction between adenosine monophosphate-activated protein kinase and the insulin signaling pathway in 3T3-L1adipocytes", Int J Mol Med, 30, pp.979~985 (2012)
- McInnes KJ, "Regulation of LKB1expression by sex hormones in adipocytes", Int J Obes (Lond), 36, pp.982~985 (2012)
- Kim JY, "Parenteral 17beta-estradiol decreases fasting blood glucose levels in non-obese mice with short-term ovariectomy", Life Sci, 87, pp.358~366 (2010)
- Mita MM, "The molecular target of rapamycin (mTOR) as a therapeutic target against cancer", Cancer Biol Ther, 2, pp.S169~S177 (2003)
