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Breast specific anti-oestrogens
Summary
This research aims to inhibit oestrogen production specifically in breast tissue, in order to reduce the side-effects associated with current anti-oestrogen treatments for breast cancer.
Description
Most post-menopausal breast cancers are oestrogen-dependent. Anti-oestrogen treatment, whilst effective, causes significant side-effects due to blockade of oestrogen action in sites other than the breast.
Tissues that use oestrogen do so at a local, paracrine level and synthesise it themselves through the action of the enzyme aromatase.
We have identified tissue-specific mechanisms of aromatase expression in breast and other tissues, and identified a number of targets (including the nuclear receptors PPARg, RXR, LRH-1 and SHP) that could be exploited to develop breast-specific anti-oestrogen therapies.
Funding
National Health and Medical Research Council
Victorian Breast Cancer Research Consortium
Selected Publications
McInnes KJ, Brown KA, Knower KC, Chand AL, Clyne CD, Simpson ER (2008). Characterisation of aromatase expression in the human adipocyte cell line SGBS. Breast Cancer Res Treat 112:429-435
Safi R, Kovacic A, Gaillard S, Murata Y, Simpson ER, McDonnell DP, Clyne CD. (2005). Coactivation of liver receptor homologue-1 by peroxisome proliferator-activated receptor gamma coactivator-1alpha on aromatase promoter II and its inhibition by activated retinoid X receptor suggest a novel target for breast-specific antiestrogen therapy. Cancer Res 65:11762-70
Kovacic A, Speed CJ, Simpson ER, Clyne CD (2004) Inhibition of aromatase transcription via promoter II by Short Heterodimer Partner (SHP) in human preadipocytes. Mol Endocrinol 18:252-259
Sofi M, Young MJ, Simpson ER, Clyne CD (2003) Regulation of promoter II-specific CYP19 transcription by CREB in breast preadipocytes. Breast Cancer Res Treat 79:399-407
Kuruppu,D, Kalus A, Simpson ER, Clyne CD (2002) Aromatase and prostaglandin inter-relationships in breast adipose tissue: significance for breast cancer development. Breast Cancer Res Treat 76:103-109
Rubin GL, Duong JH, Clyne CD, Speed CJ, Gong CH, Simpson ER (2002) Ligands for the peroxisome proliferator-activated receptor and the retinoid X receptor inhibit P450 aromatase (CYP19) expression mediated by promoter II in human breast adipose. Endocrinology 143:2863-2871