Dietary lariciresinol attenuates mammary tumor growth and reduces blood vessel density in human MCF‐7 breast cancer xenografts and carcinogen‐induced mammary tumors in rats

2008 ◽  
Vol 123 (5) ◽  
pp. 1196-1204 ◽  
Author(s):  
Niina M. Saarinen ◽  
Anni Wärri ◽  
Ruud P.M. Dings ◽  
Maarit Airio ◽  
Annika I. Smeds ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Blood Vessel ◽  
Tumor Growth ◽  
Mammary Tumor ◽  
Mammary Tumors ◽  
Vessel Density ◽  
Blood Vessel Density ◽  
Mammary Tumor Growth ◽  
Breast Cancer Xenografts ◽  
Mcf 7

scholarly journals Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression

2008 ◽  
Vol 199 (2) ◽  
pp. 221-233 ◽  
Author(s):  
Candida N Perera ◽  
Hwei G Chin ◽  
Nadire Duru ◽  
Ignacio G Camarillo
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Growth Factor ◽  
Tumor Growth ◽  
Mammary Tumor ◽  
Breast Cancer Cells ◽  
Breast Cancer Incidence ◽  
Mammary Tumor Growth ◽  
Apoptotic Genes ◽  
Mcf 7

Obesity is a recently established risk factor for breast cancer incidence and mortality. A characteristic of obesity is elevated circulating levels of adipocyte-derived hormone leptin. Evidence indicates that leptin plays an important role in mammary tumor formation; however, the mechanisms involved are poorly understood. Toward better defining the role of leptin in breast cancer, we describe the identification of leptin-regulated genes in hormone-responsive Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells using a microarray system. More than 64 leptin-regulated genes were identified including those for growth factors, cell cycle regulators, extracellular matrix (ECM) proteins, and genes associated with metastasis. Cell cycle genes up-regulated by leptin include cyclins D and G, cyclin-dependent kinase 2, p21, p27, and p16. Leptin suppressed the expression of transforming growth factor-β , a cell cycle suppressor. Determining the significance of this effect, treatment of MCF-7 cells with TGFB1 abrogated leptin-stimulated proliferation. Leptin up-regulated the expression of connective tissue growth factor, villin 2, and basigin, factors that are associated with ECM and are known to impact tumor growth. Finally, leptin induced the expression of anti-apoptotic genes BCL2 and survivin, and reduced the expression of apoptotic genes. The effect of leptin on MCF-7 survival was evaluated via TUNEL assay and demonstrated a sixfold reduction in apoptosis in leptin-treated cells, compared with controls. These data suggest leptin promotes mammary tumor growth through multiple mechanisms, including regulating the cell cycle, apoptosis, and by modulating the extracellular environment. The identification of leptin-regulated genes begins to provide mechanistic links into the relationship between obesity and breast cancer incidence and morbidity.

Abstract B106: Nedd9 null status initially delays mammary tumor growth, then selects for hyper‐aggressive mammary tumors

2009 ◽  
Author(s):  
Mahendra K. Singh ◽  
Eugene Izumchenko ◽  
Andres JP Klein‐Szanto ◽  
Erica A. Golemis
Keyword(s):  
Tumor Growth ◽  
Mammary Tumor ◽  
Mammary Tumors ◽  
Mammary Tumor Growth

scholarly journals IGF1 dependence of dietary energy balance effects on murine Met1 mammary tumor progression, epithelial-to-mesenchymal transition, and chemokine expression

2012 ◽  
Vol 20 (1) ◽  
pp. 39-51 ◽  
Author(s):  
Nikki A Ford ◽  
Nomeli P Nunez ◽  
Valerie B Holcomb ◽  
Stephen D Hursting
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Mammary Tumor ◽  
Murine Model ◽  
Epithelial To Mesenchymal Transition ◽  
Luminal Breast Cancer ◽  
Growth Factor Signaling ◽  
Mesenchymal Transition ◽  
Chemokine Expression ◽  
Mammary Tumor Growth

Luminal breast tumors with little or no estrogen receptor α expression confer poor prognosis. Using the Met1 murine model of luminal breast cancer, we characterized the IGF1-dependency of diet-induced obesity (DIO) and calorie restriction (CR) effects on tumor growth, growth factor signaling, epithelial-to-mesenchymal transition (EMT), and chemokine expression. Liver-specific IGF1-deficient (LID) and littermate control (LC) mice were administered control, DIO, or 30% CR diets for 3 months before orthotopic injection of Met1 cells. Tumors grew for 1 month and then were assessed for Akt pathway activation and mRNA expression of chemokine and EMT constituents. LID mice, regardless of diet, displayed reduced Met1 tumor growth and downregulated Akt, EMT, and chemokine pathways. CR, relative to control, reduced serum IGF1 and Met1 tumor growth in LC (but not LID) mice. DIO, relative to control, increased Met1 tumor growth and chemokine expression in LID mice, and had no effect on serum IGF1 or pAkt or cyclin D1 expression in either genotype. Thus, circulating IGF1 (in association with Akt, EMT, and chemokines) regulated Met1 tumor growth. While the anticancer effects of CR were largely IGF1-dependent, the procancer effects of DIO manifested only when circulating IGF1 levels were low. Thus, in a murine model of luminal breast cancer, IGF1 and its downstream signaling pathway, EMT, and chemokines present possible mechanistic regulatory targets. Transplanted MMTV1 Wnt1 mammary tumor growth was also reduced in LID mice, relative to LC mice, suggesting that the IGF1 effects on mammary tumor growth are not limited to Met1 tumors.

scholarly journals Should diabetic women with breast cancer have their own intervention studies?

2011 ◽  
Vol 19 (1) ◽  
pp. C13-C17
Author(s):  
David A Potter ◽  
Douglas Yee ◽  
Zhijun Guo ◽  
Mariangellys Rodriguez
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Tumor Growth ◽  
Calorie Restriction ◽  
Mammary Tumor ◽  
Intervention Studies ◽  
Diabetic Mouse ◽  
Mouse Mammary Tumor ◽  
Mammary Tumor Growth ◽  
Postmenopausal Obesity

This commentary on ‘Calorie restriction and rapamycin inhibit MMTV-Wnt-1 mammary tumor growth in a mouse model of postmenopausal obesity’ by Nogueiraet al., published in this issue ofEndocrine-Related Cancer, addresses the challenges of translating diet, exercise, and pharmacologic trials in diabetic mouse mammary tumor models to human studies. We propose that trials specifically designed to test such interventions in diabetic women with breast cancer would be valuable and informative.

scholarly journals Calorie restriction and rapamycin inhibit MMTV-Wnt-1 mammary tumor growth in a mouse model of postmenopausal obesity

2011 ◽  
Vol 19 (1) ◽  
pp. 57-68 ◽  
Author(s):  
Leticia M Nogueira ◽  
Sarah M Dunlap ◽  
Nikki A Ford ◽  
Stephen D Hursting
Keyword(s):  
Breast Cancer ◽  
Energy Balance ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Calorie Restriction ◽  
Mammary Tumor ◽  
Treadmill Exercise ◽  
Mammary Tumor Growth ◽  
Postmenopausal Obesity ◽  
Ad Libitum

Obesity is an established risk and progression factor for postmenopausal breast cancer. Interventions to decrease caloric intake and/or increase energy expenditure beneficially impact tumor progression in normoweight humans and animal models. However, despite the increasingly high global prevalence of obesity, the effects and underlying mechanisms of these energy balance modulating interventions are poorly characterized in obese individuals. The goal of this study was to better characterize the mechanism(s) responsible for the link between energy balance and breast cancer progression in the postmenopausal obesity context. We compared the effects of calorie restriction (CR), treadmill exercise (EX), and mammalian target of rapamycin (mTOR inhibitor) treatment on body composition, serum biomarkers, cellular signaling, and mammary tumor growth in obese mice. Ovariectomized C57BL/6 mice were administered a diet-induced obesity regimen for 8 weeks, then randomized into three treatment groups: control (semipurified diet fedad libitum, maintained the obese state); 30% CR (isonutrient relative to control except 30% reduction in carbohydrate calories); and EX (control diet fedad libitumplus treadmill exercise). Mice were implanted with syngeneic MMTV-Wnt-1 mammary tumor cells at week 12. Rapamycin treatment (5 mg/kg every 48 h) started at week 14. Tumors were excised at week 18. CR and rapamycin (but not EX) significantly reduced final tumor weight compared to control. In follow-up analysis, constitutive activation of mTOR ablated the inhibitory effects of CR on Wnt-1 mammary tumor growth. We conclude that mTOR inhibition may be a pharmacologic strategy to mimic the anticancer effects of CR and break the obesity–breast cancer progression link.

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