Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Androgen receptor activation inhibits in vitro migration of estrogen receptor-positive breast cancer cells (#504)

Dana B Al Safadi 1 , Michael L De Ieso 1 , Carmela Ricciardelli 1 2 , Amy R Dwyer 1 , Wayne D Tilley 1 , Theresa E Hickey 1
  1. Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
  2. The Reproductive Cancer Group, Adelaide Medical School, Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia

Currently there are limited treatments available for metastatic breast cancer which accounts for 90% of breast cancer mortality (1). Our laboratory has identified that the androgen receptor (AR) acts as a tumour suppressor in estrogen receptor positive (ER+) breast cancer (2). AR agonists effectively inhibited growth of ER + breast tumours but their effect on metastasis is unknown. The aim of this study was to investigate whether AR activation could influence the migration of ER+ breast cancer cells in vitro.

MCF7-tet-AR1-707aa, a derivative of the ER+ MCF7 cell line with doxycycline-inducible expression of a constitutively active AR (2), and the ER+AR+ BT474 cell line treated with androgen (5α-dihydrotestosterone; DHT), were used to assess the effect of AR activation on cancer cells in transwell-migration assays. Epidermal growth factor (EGF) and fetal bovine serum (FBS) were used as chemoattractants. Expression of ER, AR, EGF-Receptor (EGFR) and an epithelial marker (E-cadherin) was determined by Western blotting.

Induction of constitutively active AR had no effect on MCF7-tet-AR1-707 migration (n=3; P > 0.5, one-way ANOVA) but DHT treatment significantly inhibited migration of BT474 cells (61% of control with 1 nM, 51% with 5 nM, and 36.9% with 10 nM DHT; n=4; P ≤ 0.01, one-way ANOVA). Activation of AR reduced ER and had no effect on E-cadherin expression in MCF7-tet-AR1-707aa and BT474 cells. Baseline EGFR expression was undetectable in MCF7-tet-AR1-707 cells but was high in BT474 cells and significantly reduced by treatment with DHT.

Our study indicates that AR agonism has the potential to inhibit in vitro migration of AR+ER+ breast cancer cells with elevated expression of EGFR. We are now investigating additional AR+ER+ breast cancer models and undertaking mechanistic studies to determine how AR may regulate EGFR expression and whether stimulation of AR signalling inhibits metastasis in vivo.  

  1. Afifi, A.M. et al. (2019) ‘Causes of death after breast cancer diagnosis: A US population‐based analysis’, Cancer, 126(7), pp. 1559–1567. doi:10.1002/cncr.32648.
  2. Hickey, T.E. et al. (2021) ‘The androgen receptor is a tumor suppressor in estrogen receptor–positive breast cancer’, Nature Medicine, 27(2), pp. 310–320. doi:10.1038/s41591-020-01168-7.