Introduction: The steroid hormone receptor, estrogen receptor (ER), drives the growth of most breast cancers. Androgen receptor (AR) is another steroid receptor that induces secondary sexual characteristics and inhibition of breast development in boys, and inhibition of breast cancer in men. Recently it was discovered that AR can substitute for ER in a small subset of breast cancers and this has led to clinical trials inhibiting the AR, as a novel breast cancer therapy1. Thus AR appears to exhibit a duality of action, being cancer protective in certain contexts and promoting breast cancer growth in others. No avenues to stratify patients for AR-targeting therapy are available, therefore an immediate need exists to determine whether activating or inhibiting the AR is the most rational approach to breast cancer therapy.
Aims: Determine whether AR is associated with activation or inhibition of breast cancer cell proliferation at single cell resolution.
Methods: Multichannel confocal immunofluorescence to assess the expression of ER, AR and proliferation marker Ki67, in MCF7, ZR-75-1 and T47D, ER-positive breast cancer cell lines.
Results: Cells expressing highest levels of AR do not express ER or the proliferation marker Ki67. Cells expressing highest levels of ER do not express AR or the proliferation marker Ki67. Cells expressing intermediate levels of AR, ER or AR and ER are positive for Ki67. Treatment with androgens increases AR expression while treatment with estrogen decreases ER expression.
Conclusions: Distinct populations of AR- and ER-expressing cells exist in breast cancer cell lines, a pattern that is only revealed by assessment at single cell resolution. Estradiol reduces ER expression and is associated with proliferation of breast cancer cells. Androgen increases AR expression and is associated with lack of proliferation. Therefore activating the AR is a rational approach to therapy for ER-positive breast cancer.