Weight gain increases human aromatase expression in mammary gland

Dong Chen, Hong Zhao, John S. Coon, Masanori Ono, Elizabeth K. Pearson, Serdar E. Bulun*

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)114-120
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume355
Issue number1
DOIs
StatePublished - May 15 2012

Keywords

  • Aromatase
  • Breast cancer
  • Mammary
  • Obesity
  • Overweight
  • Weight gain

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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