title: Inflammation, dysregulated metabolism and aromatase in obesity and breast cancer.
abstract: Obesity is associated with an increased risk of estrogen-dependent breast cancer after menopause. Adipose tissue undergoes important changes in obesity due to excess storage of lipids, leading to adipocyte cell death and the recruitment of macrophages. The resultant state of chronic low-grade inflammation is associated with the activation of NFkB signaling and elevated levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis. This occurs not only in the visceral and subcutaneous fat, but also in the breast fat. The regulation of aromatase in the breast adipose stromal cell in response to inflammatory mediators is under the control of complex signaling pathways, including metabolic pathways involving LKB1/AMPK, p53, HIF1α and PKM2. Interventions aimed at modifying weight, including diet and exercise, are associated with changes in adipose tissue inflammation and estrogen production that are likely to impact breast cancer risk. This review will present an overview of these topics.
authors.affiliation: Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Faculty of Applied Medical Science, Taibah University, Medina, Saudi Arabia; Monash University, Clayton, Victoria, Australia.
authors.forename: Heba
authors.initials: H
authors.lastname: Zahid
authors.affiliation: Centre for Endocrinology and Metabolism, Hudson Institute for Medical Research, Clayton, Victoria, Australia; Monash University, Clayton, Victoria, Australia.
authors.forename: Evan R
authors.initials: ER
authors.lastname: Simpson
authors.affiliation: Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Monash University, Clayton, Victoria, Australia. Electronic address: kristy.brown@hudson.org.au.
authors.forename: Kristy A
authors.initials: KA
authors.lastname: Brown
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D001943:Breast Neoplasms / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D016923:Cell Death; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology* / Q000628:therapy; D050356:Lipid Metabolism; D009765:Obesity / Q000150:complications* / Q000503:physiopathology / Q000628:therapy
chemical_list: D004967:Estrogens; D001141:Aromatase