title: Activation of the MAP kinase pathway induces chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) expression in human breast cancer cell lines.
abstract: Growth factors are essential for cellular growth and differentiation in both normal and malignant human breast epithelial cells. In the present study we investigated the effect of epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha) and phorbol myristate acetate (PMA) on chicken ovalbumin upstream promoter-transcription factor (COUP-TF) expression in human breast cancer cells. The orphan receptors COUP-TFI and COUP-TFII are members of the nuclear receptor superfamily. The high degree of evolutionary conservation of these proteins strongly argues for an important biological function. COUP-TF expression was highest in SK-BR3 cells (approximately 130 amol/ micro g total RNA), while the lowest COUP-TF expression was observed in MCF-7 cells (3.5 amol/ micro g total RNA). While treatment of EGF, TGFalpha and PMA induced expression of COUP-TFII, COUP-TFI did not respond to these agents. Oncostatin M (OSM) is known to exert an antiproliferative effect in breast cancer cells. Treatment of MCF-7 cells with OSM resulted in an approximately 90% reduction of COUP-TFII mRNA expression. In SK-BR3 cells, treatment with the MEK inhibitor UO126 resulted in a profound suppression of endogenous COUP-TFII expression. Furthermore, cotreatment with UO126 prevented induction of COUP-TFII expression by EGF in MCF-7 cells. In conclusion, our data provide evidence, for the first time, that mitogenic substances which activate the MAP kinase pathway, can induce COUP-TFII expression. Our results strongly suggest that an active MAP kinase pathway is essential for COUP-TFII expression in human breast cancer cells.
authors.affiliation: First Department of Internal Medicine, Landeskliniken Salzburg, Muellner-Hauptstr 48, 5020 Salzburg, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Moré
authors.forename: T
authors.initials: T
authors.lastname: Fellner
authors.forename: H
authors.initials: H
authors.lastname: Doppelmayr
authors.forename: C
authors.initials: C
authors.lastname: Hauser-Kronberger
authors.forename: N
authors.initials: N
authors.lastname: Dandachi
authors.forename: P
authors.initials: P
authors.lastname: Obrist
authors.forename: F
authors.initials: F
authors.lastname: Sandhofer
authors.forename: B
authors.initials: B
authors.lastname: Paulweber
mesh_terms: D015153:Blotting, Western / Q000379:methods; D001943:Breast Neoplasms / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D051838:COUP Transcription Factor I; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000032:analysis / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000494:pharmacology; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D011987:Receptors, Steroid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D002070:Butadienes; D051838:COUP Transcription Factor I; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D020928:Mitogen-Activated Protein Kinases; D009570:Nitriles; D053683:Oncostatin M; D010455:Peptides; D011987:Receptors, Steroid; D013755:Tetradecanoylphorbol Acetate; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha; C497589:NR2F1 protein, human; C508351:OSM protein, human; C113580:U 0126; C095569:NR2F2 protein, human