Weight gain increases human aromatase expression in mammary gland

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• 作者：Dong Chen ; Hong Zhao ; John S. Coon V ; Masanori Ono ; Elizabeth K. Pearson ; Serdar E. Bulun ; ^{s-bulun@northwestern.edu}
• 关键词：Aromatase ; Overweight ; Weight gain ; Obesity ; Mammary ; Breast cancer
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2012
• 期刊代码：109_03037207
• 类别：bio
• 出版时间：15 May, 2012
• 卷：355
• 期：1
• 页码：114-120
• 文件大小：471 K

摘要

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鈥?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 TNF伪 and C/EBP尾. 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.