title: Hyaluronate synthase-2 overexpression alters estrogen dependence and induces histone deacetylase inhibitor-like effects on ER-driven genes in MCF7 breast tumor cells.
abstract: In breast carcinoma cells, high levels of hyaluronan (HA) and its CD44 receptor are frequently associated with alteration in estrogen signaling. We demonstrate that stable hyaluronate synthase 2 (HAS2) overexpression in estrogen receptor α (ERα) -positive MCF7 cells oppositely altered estrogen dependence of cell growth and its sensitivity towards antiestrogens. Albeit without effect on ERα expression and estradiol binding properties, HAS2 overexpression increased ERα Ser118 phosphorylation as well as transcriptional activity of estrogen in an ERE-luciferase reporter gene assay. However, HAS2 overexpression induced partial silencing of E2 driven-genes without affecting the magnitude of regulation by estradiol. This effect was associated with half-reduction in the activity of nuclear histone deacetylases (HDACs) through a post-translational mechanism likely consecutive to the enhanced expression of the histone acetyl-transferase EP300. In conclusion, increase in HA/CD44 interactions may contribute, through an HDAC inhibitor-like and ER-independent mechanism, to the silencing of estrogen-driven genes in breast carcinoma.
authors.affiliation: Normandie Univ, UNICAEN, OeReCa, 14000 Caen, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Vanneste
authors.affiliation: Normandie Univ, UNICAEN, OeReCa, 14000 Caen, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Hanoux
authors.affiliation: Université Mohammed Premier, Faculté des Sciences, Laboratoire de Biochimie, Oujda, Morocco.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bouakka
authors.affiliation: Normandie Univ, UNICAEN, OeReCa, 14000 Caen, France. Electronic address: pierre-jacques.bonnamy@unicaen.fr.
authors.forename: Pierre-Jacques
authors.initials: PJ
authors.lastname: Bonnamy
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter; D014453:Glucuronosyltransferase / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D061986:MCF-7 Cells; D008745:Methylation / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D056572:Histone Deacetylase Inhibitors; D018960:Hyaluronan Receptors; D006877:Hydroxamic Acids; D010768:Phosphoserine; C012589:trichostatin A; D006820:Hyaluronic Acid; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases
keywords: Breast cancer; Estrogen signaling; Histone deacetylases; Hyaluronan; Hyaluronate synthase 2