Androgen Receptor Signalling Promotes a Luminal Phenotype in Mammary Epithelial Cells

Gerard Tarulli, Geraldine Laven-Law, Mona Shehata, Kirsty Walters, Denise Iza, Mohammaed Rahman, David Handelsman, Nicola Dean, Wayne Tilley, Theresa Hickey

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Abstract

Androgens influence mammary gland development but the specific role of the androgen receptor (AR) in mammary function is largely unknown. We identified cell subsets that express AR in vivo and determined the effect of AR activation and transgenic AR inhibition on sub-populations of the normal mouse mammary epithelium by flow cytometry and immunohistochemistry. Immunolocalisation of AR with markers of lineage identity was also performed in human breast tissues. AR activation in vivo significantly decreased the proportion of basal cells, and caused an accumulation of cells that expressed a basal cell marker but exhibited morphological features of luminal identity. Conversely, in AR null mice the proportion of basal mammary epithelial cells was significantly increased. Inhibition of AR increased basal but not luminal progenitor cell activity in vitro. A small population of AR-positive cells in a basal-to-luminal phenotype transition was also evident in human breast lobules. Collectively, these data support a role for AR in promoting a luminal phenotype in mammary epithelial cells.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalJOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
Volume24
Issue number1
DOIs
Publication statusPublished - 15 Mar 2019

Keywords

  • Androgen receptor
  • Androgens
  • Mammary epithelium

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    Tarulli, G., Laven-Law, G., Shehata, M., Walters, K., Iza, D., Rahman, M., Handelsman, D., Dean, N., Tilley, W., & Hickey, T. (2019). Androgen Receptor Signalling Promotes a Luminal Phenotype in Mammary Epithelial Cells. JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA, 24(1), 99-108. https://doi.org/10.1007/s10911-018-9406-2