title: A novel function of the Fe65 neuronal adaptor in estrogen receptor action in breast cancer cells.
abstract: Fe65 is a multidomain adaptor with established functions in neuronal cells and neurodegeneration diseases. It binds to the C terminus of the Aβ amyloid precursor protein and is involved in regulating gene transcription. The present studies show that Fe65 is expressed in breast cancer (BCa) cells and acts as an ERα transcriptional coregulator that is recruited by 17β-estradiol to the promoters of estrogen target genes. Deletion analyses mapped the ERα binding domain to the phosphotyrosine binding domain 2 (PTB2). Ectopic Fe65 increased the transcriptional activity of the ERα in a PTB2-dependent manner in reporter assays. Fe65 knockdown decreased, whereas its stable expression increased the transcriptional activity of endogenous ERα in BCa cells and the ability of estrogens to stimulate target gene expression, ERα, and coactivator recruitment to target gene promoters and cell growth. Furthermore, Fe65 expression decreased the antagonistic activity of tamoxifen (TAM), suggesting a role for Fe65 in TAM resistance. Overall, the studies define a novel role for the neuronal adaptor in estrogen actions in BCa cells.
authors.affiliation: From the Departments of Pathology and Cell Biology and.
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Sun
authors.forename: Ravi
authors.initials: R
authors.lastname: Kasiappan
authors.forename: Jinfu
authors.initials: J
authors.lastname: Tang
authors.forename: Panida L
authors.initials: PL
authors.lastname: Webb
authors.forename: Waise
authors.initials: W
authors.lastname: Quarni
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhang
authors.forename: Wenlong
authors.initials: W
authors.lastname: Bai
mesh_terms: D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: C091042:APBB1 protein, human; C506487:ESR1 protein, human; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D004967:Estrogens; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D013629:Tamoxifen; D004958:Estradiol
keywords: Breast Cancer, Estrogens, Estrogen Receptor, Fe65, Tamoxifen; Cancer Biology; Cell Growth; DNA Transcription; Endocrinology; Gene Transcription; Hormone Receptors; Hormones; Nuclear Receptors