title: Loss of Hypermethylated in Cancer 1 (HIC1) in breast cancer cells contributes to stress-induced migration and invasion through β-2 adrenergic receptor (ADRB2) misregulation.
abstract: The transcriptional repressor HIC1 (Hypermethylated in Cancer 1) is a tumor suppressor gene inactivated in many human cancers including breast carcinomas. In this study, we show that HIC1 is a direct transcriptional repressor of β-2 adrenergic receptor (ADRB2). Through promoter luciferase activity, chromatin immunoprecipitation (ChIP) and sequential ChIP experiments, we demonstrate that ADRB2 is a direct target gene of HIC1, endogenously in WI-38 cells and following HIC1 re-expression in breast cancer cells. Agonist-mediated stimulation of ADRB2 increases the migration and invasion of highly malignant MDA-MB-231 breast cancer cells but these effects are abolished following HIC1 re-expression or specific down-regulation of ADRB2 by siRNA treatment. Our results suggest that early inactivation of HIC1 in breast carcinomas could predispose to stress-induced metastasis through up-regulation of the β-2 adrenergic receptor.
authors.affiliation: CNRS UMR 8161, CNRS-Université de Lille 1-Institut Pasteur de Lille, Lille 59021, France.
authors.forename: Gaylor
authors.initials: G
authors.lastname: Boulay
authors.forename: Nicolas
authors.initials: N
authors.lastname: Malaquin
authors.forename: Ingrid
authors.initials: I
authors.lastname: Loison
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Foveau
authors.forename: Capucine
authors.initials: C
authors.lastname: Van Rechem
authors.forename: Brian R
authors.initials: BR
authors.lastname: Rood
authors.forename: Albin
authors.initials: A
authors.lastname: Pourtier
authors.forename: Dominique
authors.initials: D
authors.lastname: Leprince
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000172:deficiency / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics
chemical_list: C553443:ADRB2 protein, human; C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D018343:Receptors, Adrenergic, beta-2