We have identified and characterized a novel human estrogen receptor (ER) β isoform, ERβcx, which is truncated at the C-terminal region but has an extra 26 amino acids due to alternative splicing. The ERβcx transcript is expressed in testis, ovary, thymus and prostate as well as in human cultured cell lines such as HEC-1, HOS-TE85 and Saos-2 cells. ERβcx protein is also immunodetectable in these human cells. Biochemical analysis reveals that the average dissociation constants ( K d) of ERα and ERβ for 17β-estradiol (E 2 ) are 0.2 and 0.6 nM respectively, but ERβcx has no ligand binding ability. ERα and ERβ proteins bind to the estrogen response element, whereas ERβcx does not form any shifted complex in gel shift assays. In a transient expression assay, ERβcx shows no ligand-dependent transactivation ability of a basal promoter and also cannot interact with a cofactor, TIF1α, in the presence or absence of E 2 . ERβcx preferentially forms a heterodimer with ERα rather than that with ERβ, inhibiting DNA binding by ERα. Interestingly, however, it shows a significant dominant negative activity only against ERα transactivation. Thus, this study indicates that ERβcx potentially inhibits ERα-mediated estrogen action and that alternative splicing of the C-terminal region and its inhibitory properties are characteristic of several members of nuclear receptor isoforms.

Molecular cloning and characterization of human estrogen receptor betacx: a potential inhibitor ofestrogen action in human