Epigenetics & aromatase expression in the breast

Summary

We are investigating the role of methylation, demethylation events occurring in the various aromatase promoters to determine the importance of this in the regulation of aromatase expression within the human breast.

Description

Outcomes

Funding

NHMRC
VBCRC
Canadian Fellowship

Selected Publications

Brown KA, McInnes KJ, Hunger NI, Oakhill JS, Steinberg GR, Simpson ER. The subcellular localisation of CRTC2 provides a link between obesity and breast cancer in postmenopausal women. Cancer Res (In Press) 2009

Mahendroo MS, CR Mendelson and ER Simpson: Tissue-specific and hormonally-controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue. J Biol Chem 268:19463-19470 (1993).

Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpson ER. Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med 337(2)91-95 1997.

Jones MEE, AW Thorburn, KL Britt, KN Hewitt, NG Wreford, J Proietto, OK Oz, BJ Leury, KM Robertson, S Yao ER Simpson. Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. PNAS 97:12735-12740, 2000

Clyne CD, Speed CJ, Zhou J, Simpson ER. Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes. J Biol Chem 277:20591-20597, 2002

Britt KL, Kerr J, O'Donnell L, Jones MEE, Drummond AE, Davis SR, Simpson ER, Findlay JK. Estrogen regulates development of the somatic cell phenotype in the eutherian ovary. FASEB J 16:1389-1397 2002

Safi R, Kovacic A, Gaillard S, Murata Y, Simpson ER, McDonnell DP, Clyne CD. Coactivation of liver receptor homologue-1 by peroxisome proliferators-activated receptor gamma coactivator-1 alpha on aromatase promoter II and its inhibition by activated retinoid X receptor suggest a novel target for breast-specific antiestrogen therapy. Cancer Res 65(24):11762-11770 2005

McInnes KJ, Corbould A, Simpson ER, Jones ME. Regulation of AMPK and lipogenesis by androgens contributes to visceral obesity in an estrogen deficient state. Endocrinology 147: 5907-5913 (2006).