Promoter-specific effects of metformin on aromatase transcript expression

Nirukshi Udayanga Gunasinghe Samarajeewa, Seungmin Ham, Fangyuan Yang, Evan R Simpson, Kristy A Brown

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

Abstract

Phase III aromatase inhibitors (AIs) are proving successful in the treatment of hormone-dependent postmenopausal breast cancer. Side-effects associated with total body aromatase inhibition have prompted new research into the development of breast-specific AIs. The identification of tissue- and disease-specific usage of aromatase promoters has made the inhibition of aromatase at the transcriptional level an interesting approach. We have previously demonstrated that AMPK-activating drugs, including metformin, were potent inhibitors of aromatase expression in primary human breast adipose stromal cells (hASCs). This study examines the promoter-specific effects of metformin on inhibiting aromatase expression in hASCs. Tumour-associated promoters PII/PI.3 were activated using forskolin (FSK)/phorbol ester (PMA), whereas normal adipose associated promoter PI.4 was activated using dexamethasone (DEX)/tumour necrosis factor-alpha (TNFalpha). Results demonstrate that metformin significantly decreased the FSK/PMA-, but not the DEX/TNFalpha-mediated expression of total aromatase at concentrations of 10, 20, and 50muM (P
Original languageEnglish
Pages (from-to)768 - 771
Number of pages4
JournalSteroids
Volume76
Issue number8
DOIs
Publication statusPublished - 2011

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