Estrogen receptor (ER) |[beta]|1 and ER|[beta]|cx|[sol]||[beta]|2 inhibit ER|[alpha]| function differently in breast cancer cell line MCF7

摘要

Estrogen receptor (ER) plays an important role in the proliferation and progression of breast cancer. In order to explore the function of wild-type ER (ER1) and its variant form, ERcx/2, stable transformants of ER-positive breast cancer MCF7 cells with ER1 or ERcx/2 expression vector were established. Constitutive expression of ER1 or ERcx/2 reduced the Sphase 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 ER1 transformants were observed in the electrophoretic mobility shift assay, while no complex was observed for ERcx/2 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 ER1 and ERcx/2 transformants compared with parental cells. A comprehensive gene expression analysis using our custom-made cDNA microarray showed that MCF7 and ER1 transformants had a similar gene expression profile, whereas ERcx/2 showed a distinct profile from others. These results indicate that ER1 and ERcx/2 inhibit ER function differently in MCF7 cells.