Transgenic introduction of androgen receptor into estrogen-receptor–, progesterone-receptor–, and androgen-receptor–negative breast cancer cells renders them responsive to hormonal manipulation

Abstract

Background Estrogen-receptor (ER)–, progesterone-receptor (PR)–, and androgen-receptor (AR)–negative breast cancer cells are unaffected by treatment with dehydroepiandrosterone-sulfate (DHEAS) and an aromatase inhibitor (AI). We hypothesized that cell growth would be inhibited with DHEAS/AI treatment after successful transfection of an AR expression vector. Methods ER/PR/AR–negative breast cancer cells were transfected with an AR expression vector and treated with DHEAS/AI for 2 days. Growth inhibition of these cells was compared with that of transfected cells treated with only AI or with nontransfected cells treated with DHEAS/AI. Mann-Whitney U test was used to determine statistical significance. Results Cell death rates of 53.5% ( P = .001) and 40.1% ( P = .006) were seen in transfected cells treated with DHEAS/AI compared with controls for days 1 and 2, respectively. Nontransfected cells were unaffected by treatment. Comments ER/PR/AR–negative cells transfected with AR were killed by DHEAS/AI treatment, providing evidence that AR is responsible for this effect. This provides the first AR-targeted hormonal therapy for ER breast cancer.