Putative functional characteristics of human estrogen receptor-beta isoforms.
Estrogen receptors (ERalpha and ERbeta) are clearly multifaceted in terms of structure and function. Several relatively abundant ERbeta isoforms have been identified, which can be differentially expressed in various tIssues. In order to provide insight into the possible role of the ERbeta family in breast tIssue a study of the putative functions of the human (h) ERbeta1, hERbeta2 and hERbeta5 isoforms was undertaken. Only hERbeta1 was found to bind ligand, which induced conformational changes as determined by protease digestion assays. All ERbeta isoforms could bind to and bend DNA although the relative efficiency with which they bound DNA differed with hERalpha>hERbeta1>hERbeta2>>hERbeta5. All ERbeta isoforms inhibited ERalpha transcriptional activity on an estrogen-response element (ERE)-reporter gene. The relative activities were hERbeta1>hERbeta2>hERbeta5; however, only hERbeta1 had transcriptional activity of its own. Both LY117018-hERalpha and LY117018-hERbeta1 complexes alone could activate transcription on a TGF-beta3-CAT gene. Although hERbeta2 and hERbeta5 had no activity alone, they inhibited ERalpha but not hERbeta1 transcriptional activity of transforming growth factor (TGF)-beta3-CAT. In marked contrast to activity on an ERE-CAT reporter gene, hERbeta1 did not modulate ERalpha transcriptional activity on a TGF-beta3-CAT reporter gene. These data support promoter-specific differential activities of hERbeta isoforms with respect to models of ERalpha regulated gene expression, and suggest that they may have a role in differentially modulating estrogen action.
Peng
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B
Department of Biochemistry and Medical Genetics and the Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada R3E 0V9.
Lu
B
B
Leygue
E
E
Murphy
L C
LC
D001483:Base Sequence; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D017931:DNA Primers; D018076:DNA, Complementary; D024202:Electrophoretic Mobility Shift Assay; D047629:Estrogen Receptor beta; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D018076:DNA, Complementary; D047629:Estrogen Receptor beta; D020033:Protein Isoforms; D011960:Receptors, Estrogen