Estrogen receptor (ER) α plays an important role in the proliferation and progression of breast cancer. In order to explore the function of wild-type ERβ (ERβ1) and its variant form, ERβcx/β2, stable transformants of ERα-positive breast cancer MCF7 cells with ERβ1 or ERβcx/β2 expression vector were established. Constitutive expression of ERβ1 or ERβcx/β2 reduced the S phase population of the cell cycle in dish culture and the number of colonies in an anchorage-independent assay. DNA-protein complexes of ERE with nuclear extracts from ERβ1 transformants were observed in the electrophoretic mobility shift assay, while no complex was observed for ERβcx/β2 transformants. Reporter gene assay using estrogen-responsive element (ERE)-luciferase showed less responsiveness to estrogen in these transformants compared with parental cells. Endogenous mRNA expression of two known estrogen-responsive genes, cathepsin D and IGFBP4, was weakly induced by estrogen in ERβ1 and ERβcx/β2 transformants compared with parental cells. A comprehensive gene expression analysis using our custom-made cDNA microarray showed that MCF7 and ERβ1 transformants had a similar gene expression profile, whereas ERβcx/β2 showed a distinct profile from others. These results indicate that ERβ1 and ERβcx/β2 inhibit ERα function differently in MCF7 cells.
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