title: A novel isoform of rat estrogen receptor beta with 18 amino acid insertion in the ligand binding domain as a putative dominant negative regular of estrogen action.
abstract: A novel isoform of rat estrogen receptor (ER) beta, ER beta 2, which is a putative alternative splicing product of the reported ER beta (ER beta 1) has been identified. Rat ER beta 2 cDNA contains an additional, in-frame 54 base pair insertion in the ligand binding domain of ER beta 1, which generates an 18 amino acid residue insertion. Northern blot and RT-PCR analyses revealed that ER beta 2 coexists with ER alpha and ER beta 1 in all tissues examined including brain, lung, liver, kidney, fat, bone, uterus, prostate, and ovary. The insertion caused loss of ligand binding activity of ER beta 2, whereas the ability to bind the palindromic estrogen response element (ERE) was retained. In an ERE-containing luciferase reporter gene assay using COS-1 cells, ER beta 2 failed to activate estrogen-dependent transcription. Furthermore, ER beta 2 dose dependently suppressed the ER alpha- and ER beta 1-mediated transcriptional activation. These results suggest that rat ER beta 2 functions as a negative regulator of estrogen action.
authors.affiliation: Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: H
authors.initials: H
authors.lastname: Endoh
authors.forename: H
authors.initials: H
authors.lastname: Sasaki-Iwaoka
authors.forename: H
authors.initials: H
authors.lastname: Kanou
authors.forename: E
authors.initials: E
authors.lastname: Shimaya
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Kawashima
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D051381:Rats; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D015533:Transcriptional Activation
chemical_list: D018076:DNA, Complementary; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen