Abstract
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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Acknowledgements
We thank Ms Akiyo Yamashita for her excellent technical support. This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, for Scientific Research Expenses for Health and Welfare Programs and the Foundation for the Promotion of Cancer Research, and by the Second-Term Comprehensive 10-Year Strategy for Cancer Control.
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Omoto, Y., Eguchi, H., Yamamoto-Yamaguchi, Y. et al. Estrogen receptor (ER) β1 and ERβcx/β2 inhibit ERα function differently in breast cancer cell line MCF7. Oncogene 22, 5011–5020 (2003). https://doi.org/10.1038/sj.onc.1206787
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DOI: https://doi.org/10.1038/sj.onc.1206787
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