Effects of high fat diet-induced obesity on mammary tumorigenesis in the PyMT/MMTV murine model

Autor: Taryn L. Cranford, Meredith S. Carson, Kandy T. Velázquez, Rebecca R. Bellone, Reilly T. Enos, Mitzi Nagarkatti, Ioulia Chatzistamou, E. Angela Murphy, Alexander T Sougiannis, Jackie E. Bader
Rok vydání: 2018
Předmět:
0301 basic medicine
obesity
Aging
Cancer Research
Carcinogenesis
Mammary gland
Adipose tissue
Inbred C57BL
medicine.disease_cause
Mice
Breast cancer
0302 clinical medicine
hormone status
2.1 Biological and endogenous factors
Aetiology
Aromatase
Cancer
biology
medicine.anatomical_structure
Oncology
Hormone receptor
Risk factors for breast cancer
030220 oncology & carcinogenesis
Molecular Medicine
Female
Inflammation Mediators
Research Paper
Oncology and Carcinogenesis
Diet
High-Fat
high-fat-diet
Experimental
03 medical and health sciences
medicine
Animals
mouse models
Oncology & Carcinogenesis
Obesity
Metabolic and endocrine
Nutrition
Pharmacology
Inflammation
Animal
business.industry
Mammary Neoplasms
Mammary Neoplasms
Experimental
Estrogen
mammary tumorigenesis
Diet
Mice
Inbred C57BL
High-Fat
Disease Models
Animal
030104 developmental biology
Tumor progression
Disease Models
biology.protein
Cancer research
business
Hormone
Zdroj: Cancer biology & therapy, vol 20, iss 4
ISSN: 1555-8576
Popis: Clinical studies provide strong evidence that obesity and associated adipose tissue (AT) inflammation are risk factors for breast cancer (BrCA); however, mechanistic knowledge of the interaction of obesity, BrCA, and menopausal status has proven to be not only lacking, but contradictory. Obesity-induced inflammation and elevated biosynthesis of estrogens, through aromatase-mediated metabolism of precursors, have been linked with hormone receptor positive (HP) postmenopausal BrCA but not previously associated with premenopausal BrCA risk. Thus, further delineation of the interaction of obesity, inflammation, and aromatase is required for the development of therapeutic treatment options. The purpose of this study was to examine the effect of high fat diet (HFD)-induced inflammation on tumorigenesis in a model of pre and postmenopausal HP BrCA. Female PyMT/MMTV ovary intact and ovariectomized mice were fed low and HFD diets to examine the role of obesity-induced inflammation and hormone production in the development of HP BrCA. Tumor statistics for number, volume, weight, histopathology scoring and gene expression of macrophage and inflammatory mediators were measured in the AT and mammary gland at sacrifice. HFD feedings of ovary intact mice resulted in increased adiposity and tumorigenesis, indicated by increased primary tumor volume, multiplicity, tumor burden, and increased tumor progression represented by histopathological scoring. HFD-induced obesity significantly upregulated aromatase and macrophage marker expression in the AT (F4/80 and CD11c) and mammary gland (Mertk) in a premenopausal model of BrCA. Conversely, HFD feedings had no significant effect on tumorigenesis in a postmenopausal model of BrCA despite large increases in adiposity in ovariectomized mice; however, limitations within the model may have precluded any significant findings. This data suggests that obesity-induced increases in inflammation and hormone production, via aromatase expression, is associated with increases in tumorigenesis in a model of premenopausal HP BrCA in the PyMT/MMTV strain.
Databáze: OpenAIRE
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