When
estrogen binds its receptor (ER), it becomes a potent
mitogen in a number of target tissues including the mammary gland where it plays an important role in the pathogenesis of mammary
carcinoma.
Arsenic trioxide (
AS2O3), a clinically effective agent against
acute promyelocytic leukemia, has been shown to induce apoptosis in a variety of
cancer cells in vitro. Here, we investigated the effects of
AS2O3 on the growth of two ER-positive
breast cancer cell lines, MCF7 and T47D in vitro. We found that higher doses of
AS2O3 dramatically reduced the survival of these two
breast cancer cell lines while lower doses of
AS2O3 significantly inhibited the expression of
estrogen receptor alpha (ER-alpha), but did not effect ER-beta expression. The ER-alpha expression is totally restored when
AS2O3 is absent for 24 hours. Using a reporter gene controlled by ER, we further demonstrated that
AS2O3 strongly-repressed 17beta-estradiol (E2) stimulated-transcriptional activation. Moreover,
AS2O3 abolished transcriptional induction of the
estrogen responsive gene pS2 mediated by E2. These results indicated that
AS2O3 specifically inhibits expression and signaling pathway of the ER-alpha. We suggest that
AS2O3 in combination with other methods might provide a novel therapeutic approach for ER-alpha-positive
breast cancer.