title: Weight gain increases human aromatase expression in mammary gland.
abstract: Adulthood weight gain predicts estrogen receptor-positive breast cancer. Because local estrogen excess in the breast likely contributes to cancer development, and aromatase is the key enzyme in estrogen biosynthesis, we investigated the role of local aromatase expression in weight gain-associated breast cancer risk in a humanized aromatase (Arom(hum)) mouse model containing the coding region and the 5'-regulatory region of the human aromatase gene. Compared with littermates on normal chow, female Arom(hum) mice on a high fat diet gained more weight, and had a larger mammary gland mass with elevated total human aromatase mRNA levels via promoters I.4 and II associated with increased levels of their regulators TNFα and C/EBPβ. There was no difference in total human aromatase mRNA levels in gonadal white adipose tissue. Our data suggest that diet-induced weight gain preferentially stimulates local aromatase expression in the breast, which may lead to local estrogen excess and breast cancer risk.
authors.affiliation: Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: John S
authors.initials: JS
authors.lastname: Coon
authors.forename: Masanori
authors.initials: M
authors.lastname: Ono
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Pearson
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006066:Gonads / Q000378:metabolism; D006801:Humans; D008321:Mammary Glands, Animal / Q000201:enzymology* / Q000473:pathology; D042361:Mammary Glands, Human / Q000201:enzymology / Q000473:pathology; D051379:Mice; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D004967:Estrogens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D001141:Aromatase