TY - JOUR
T1 - Promoter-specific effects of metformin on aromatase transcript expression
AU - Samarajeewa, Nirukshi Udayanga Gunasinghe
AU - Ham, Seungmin
AU - Yang, Fangyuan
AU - Simpson, Evan R
AU - Brown, Kristy A
PY - 2011
Y1 - 2011
N2 - 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
AB - 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
UR - http://www.ncbi.nlm.nih.gov/pubmed/21414336
U2 - 10.1016/j.steroids.2011.02.041
DO - 10.1016/j.steroids.2011.02.041
M3 - Article
VL - 76
SP - 768
EP - 771
JO - Steroids
JF - Steroids
SN - 0039-128X
IS - 8
ER -
