Estrogen receptor β inhibits 17β-estradiol-stimulated proliferation of the breast cancer cell line T47D

Estrogen receptor (ER) β counteracts the activity of ERα in many systems. In agreement with this, we show in this study that induced expression of ERβ in the breast cancer cell line T47D reduces 17β-estradiol-stimulated proliferation when expression of ERβ mRNA equals that of ERα. Induction of ERβ reduces growth of exponentially proliferating cells with a concomitant decrease in components of the cell cycle associated with proliferation, namely cyclin E, Cdc25A (a key regulator of Cdk2), p45^Skp2 (a key regulator of p27^Kip1 proteolysis), and an increase in the Cdk inhibitor p27^Kip1. We also observed a reduced Cdk2 activity. These findings suggest a possible role for ERβ in breast cancer and imply that ERβ-specific ligands may reduce proliferation of ER-positive breast cancer cells through actions on the G₁ phase cell-cycle machinery.