title: Estrogen receptor (ER) beta1 and ERbetacx/beta2 inhibit ERalpha function differently in breast cancer cell line MCF7.
abstract: Estrogen receptor (ER) alpha plays an important role in the proliferation and progression of breast cancer. In order to explore the function of wild-type ERbeta (ERbeta1) and its variant form, ERbetacx/beta2, stable transformants of ERalpha-positive breast cancer MCF7 cells with ERbeta1 or ERbetacx/beta2 expression vector were established. Constitutive expression of ERbeta1 or ERbetacx/beta2 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 ERbeta1 transformants were observed in the electrophoretic mobility shift assay, while no complex was observed for ERbetacx/beta2 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 ERbeta1 and ERbetacx/beta2 transformants compared with parental cells. A comprehensive gene expression analysis using our custom-made cDNA microarray showed that MCF7 and ERbeta1 transformants had a similar gene expression profile, whereas ERbetacx/beta2 showed a distinct profile from others. These results indicate that ERbeta1 and ERbetacx/beta2 inhibit ERalpha function differently in MCF7 cells.
authors.affiliation: Division of Endocrinology, Saitama Cancer Center Research Institute, 818 Komuro, Ina, Saitama 362-0806, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Omoto
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Eguchi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yamamoto-Yamaguchi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hayashi
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen