The purpose of this study was to explore the role of
transcription factor Ets1 in
estrogen receptor α (ERα)-positive
breast cancer progression. We expressed human Ets1 or empty vector in four human ERα-positive
breast cancer cell lines and observed increased colony formation. Further examination of cellular responses in stable Ets1-expressing MCF7 clones displayed increased proliferation, migration, and invasion. Ets1-expressing MCF7
tumors grown in the mammary fat pads of nude mice exhibited increased rates of
tumor growth (7.36±2.47 mm(3)/day) compared to control MCF7
tumors (2.52±1.70 mm(3)/day), but maintained their dependence on
estradiol for
tumor growth. Proliferation marker Ki-67 staining was not different between control and Ets1-expressing
tumors, but Ets1-expressing
tumors exhibited large necrotic centers and elevated apoptotic staining. Ets1 was shown to cooperate with ERα and the p160
nuclear receptor coactivator (NCOA/SRC) family to increase activation of a consensus
estrogen response element
luciferase reporter construct. Ets1-expressing MCF7 cells also exhibited elevated expression of the ERα target genes,
progesterone receptor and
trefoil factor 1. Using GST-pulldown assays, Ets1 formed stable complexes containing both ERα and p160
nuclear receptor coactivators. Taken together, these data suggest that the Ets1-dependent
estradiol sensitization of
breast cancer cells and
tumors may be partially due to the ability of Ets1 to cooperate with ERα and
nuclear receptor coactivators to stimulate transcriptional activity of
estrogen-dependent genes.