Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/91293
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Type: Journal article
Title: Bringing androgens up a NOTCH in breast cancer
Author: Tarulli, G.
Butler, L.
Tilley, W.
Hickey, T.
Citation: Endocrine-Related Cancer, 2014; 21(4):T183-T202
Publisher: BioScientifica
Issue Date: 2014
ISSN: 1351-0088
1479-6821
Statement of
Responsibility: 
Gerard A Tarulli, Lisa M Butler, Wayne D Tilley and Theresa E Hickey
Abstract: While it has been known for decades that androgen hormones influence normal breast development and breast carcinogenesis, the underlying mechanisms have only been recently elucidated. To date, most studies have focused on androgen action in breast cancer cell lines, yet these studies represent artificial systems that often do not faithfully replicate/recapitulate the cellular, molecular and hormonal environments of breast tumours in vivo. It is critical to have a better understanding of how androgens act in the normal mammary gland as well as in in vivo systems that maintain a relevant tumour microenvironment to gain insights into the role of androgens in the modulation of breast cancer development. This in turn will facilitate application of androgen-modulation therapy in breast cancer. This is particularly relevant as current clinical trials focus on inhibiting androgen action as breast cancer therapy but, depending on the steroid receptor profile of the tumour, certain individuals may be better served by selectively stimulating androgen action. Androgen receptor (AR) protein is primarily expressed by the hormone-sensing compartment of normal breast epithelium, commonly referred to as oestrogen receptor alpha (ERa (ESR1))-positive breast epithelial cells, which also express progesterone receptors (PRs) and prolactin receptors and exert powerful developmental influences on adjacent breast epithelial cells. Recent lineage-tracing studies, particularly those focussed on NOTCH signalling, and genetic analysis of cancer risk in the normal breast highlight how signalling via the hormone-sensing compartment can influence normal breast development and breast cancer susceptibility. This provides an impetus to focus on the relationship between androgens, AR and NOTCH signalling and the crosstalk between ERa and PR signalling in the hormone-sensing component of breast epithelium in order to unravel the mechanisms behind the ability of androgens to modulate breast cancer initiation and growth.
Keywords: testosterone; breast; androgen receptor; hormone receptor; mammary gland
Rights: © 2014 Society for Endocrinology
RMID: 0030014555
DOI: 10.1530/ERC-14-0248
Grant ID: http://purl.org/au-research/grants/nhmrc/1008349
Appears in Collections:Medicine publications

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