Estrogen receptor (ER) beta1 and ERbetacx/beta2 inhibit ERalpha function differently in breast cancer cell line MCF7.
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.
Omoto
Yoko
Y
Division of Endocrinology, Saitama Cancer Center Research Institute, 818 Komuro, Ina, Saitama 362-0806, Japan.
Eguchi
Hidetaka
H
Yamamoto-Yamaguchi
Yuri
Y
Hayashi
Shin-ichi
S
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
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen