Hypoxia Down-regulates CCAAT/Enhancer Binding Protein-α Expression in Breast Cancer Cells
| Autor: | Robert Barouki, Etienne Blanc, Nathalie M. Mazure, Fabrice Lecuru, Marie-Claude Fulchignoni-Lataud, Marie-Aude Le Frere Belda, Anne Dreiem, Thérèse Hervèe Mayi, Charbel Massaad, Vincent Favaudon, Liliane Massaad-Massade, Ramzi Seifeddine |
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| Přispěvatelé: | Laboratoire de Détection et de Géophysique (CEA) (LDG), DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), IFR50, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Faculté de Médecine Nice, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Génotoxicologie, signalisation et radiothérapie expérimentale, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique moléculaire, Régulation de la transcription et maladies génétiques (RTMG), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Stéroïdes et système nerveux : physiopathologie moléculaire et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Paris-Sud, Université Paris-Sud - Paris 11 (UP11), Toxicologie Moleculaire (U490), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire de Détection et de Géophysique (CEA) ( LDG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Faculté de Médecine Nice, Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Régulation de la transcription et maladies génétiques ( RTMG ), Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ), Toxicologie Moleculaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Faculté de Médecine Nice, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie |
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Hypoxia-Inducible Factor 1 MESH : Molecular Sequence Data MESH : RNA Messenger Transcription Genetic MESH : Immunohistochemistry MESH: Cell Hypoxia Electrophoretic Mobility Shift Assay MESH: Cell Cycle RNA polymerase II MESH : Blotting Western MESH : Breast Neoplasms MESH: Base Sequence MESH : RNA Small Interfering MESH: Down-Regulation MESH : Down-Regulation 0302 clinical medicine Transcription (biology) MESH: Reverse Transcriptase Polymerase Chain Reaction Enhancer binding MESH: RNA Small Interfering Gene expression MESH: CCAAT-Enhancer-Binding Protein-alpha MESH : CCAAT-Enhancer-Binding Protein-alpha RNA Small Interfering Promoter Regions Genetic 0303 health sciences Gene knockdown Reverse Transcriptase Polymerase Chain Reaction Cell Cycle MESH : Reverse Transcriptase Polymerase Chain Reaction Immunohistochemistry Cell Hypoxia 3. Good health MESH: Promoter Regions (Genetics) Oncology MESH : Electrophoretic Mobility Shift Assay 030220 oncology & carcinogenesis MESH: Cell Growth Processes MESH : Cell Hypoxia MESH : Transfection Subcellular Fractions medicine.medical_specialty MESH : Hypoxia-Inducible Factor 1 alpha Subunit MESH: Cell Line Tumor Blotting Western Molecular Sequence Data MESH : Deferoxamine Down-Regulation Breast Neoplasms Cell Growth Processes MESH : Subcellular Fractions Deferoxamine Biology Transfection MESH: Hypoxia-Inducible Factor 1 alpha Subunit 03 medical and health sciences Cell Line Tumor Internal medicine MESH : Cell Cycle CCAAT-Enhancer-Binding Protein-alpha medicine Humans MESH: Blotting Western [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology RNA Messenger [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology Transcription factor MESH: RNA Messenger 030304 developmental biology MESH: Humans MESH: Molecular Sequence Data Base Sequence MESH : Cell Line Tumor MESH: Transcription Genetic MESH: Transfection MESH : Humans MESH : Transcription Genetic MESH: Immunohistochemistry MESH: Deferoxamine Hypoxia-Inducible Factor 1 alpha Subunit MESH : Promoter Regions (Genetics) Molecular biology Endocrinology HIF1A MESH : Cell Growth Processes MESH: Subcellular Fractions MESH: Electrophoretic Mobility Shift Assay biology.protein MESH : Base Sequence MESH: Breast Neoplasms |
| Zdroj: | Cancer Research Cancer Research, American Association for Cancer Research, 2008, 68 (7), pp.2158-65. ⟨10.1158/0008-5472.CAN-07-1190⟩ Cancer Research, 2008, 68 (7), pp.2158-65. ⟨10.1158/0008-5472.CAN-07-1190⟩ Cancer Research, American Association for Cancer Research, 2008, 68 (7), pp.2158-65. 〈10.1158/0008-5472.CAN-07-1190〉 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | International audience; The transcription factor CCAAT/enhancer binding protein-alpha (C/EBP alpha) is involved in the control of cell differentiation and proliferation, and has been suggested to act as a tumor suppressor in several cancers. By using microarray analysis, we have previously shown that hypoxia and estrogen down-regulate C/EBP alpha mRNA in T-47D breast cancer cells. Here, we have examined the mechanism by which the down-regulation by hypoxia takes place. Using the specific RNA polymerase II inhibitor 5,6-dichlorobenzimidazole-1-beta-D-ribofuranoside, the mRNA stability was analyzed under normoxia or hypoxia by quantitative reverse transcription-PCR. Hypoxia reduced the half-life of C/EBP alpha mRNA by approximately 30%. C/EBP alpha gene promoter studies indicated that hypoxia also repressed the transcription of the gene and identified a hypoxia-responsive element (-522; -527 bp), which binds to hypoxia-inducible factor (HIF)-1 alpha, as essential for down-regulation of C/EBP alpha transcription in hypoxia. Immunocytochemical analysis showed that C/EBP alpha was localized in the nucleus at 21% O(2), but was mostly cytoplasmic under 1% O(2). Knockdown of HIF-1 alpha by RNAi restored C/EBP alpha to normal levels under hypoxic conditions. Immunohistochemical studies of 10 tumor samples did not show any colocalization of C/EBP alpha and glucose transporter 1 (used as a marker for hypoxia). Taken together, these results show that hypoxia down-regulates C/EBP alpha expression in breast cancer cells by several mechanisms, including transcriptional and posttranscriptional effects. The down-regulation of C/EBP alpha in hypoxia is mediated by HIF-1. |
| Databáze: | OpenAIRE |
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