Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg cells and normal B-lymphocytes
| Autor: | Fabienne Meggetto, Alan Bénard, Nadine Cogne, Aurélie Chanut, Nathalie Faumont, Georges Delsol, Jean Feuillard |
|---|---|
| Přispěvatelé: | Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Centre de Physiopathologie Toulouse Purpan, Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH : Cell Line
MESH : Molecular Sequence Data DNA Mutational Analysis MESH: NF-kappa B Apoptosis MESH: Base Sequence medicine.disease_cause 0302 clinical medicine MESH : Tumor Cells Cultured MESH: Luciferases Renilla immune system diseases hemic and lymphatic diseases MESH : Hodgkin Disease Tumor Cells Cultured [ SDV.IMM ] Life Sciences [q-bio]/Immunology MESH: Animals MESH : Viral Matrix Proteins MESH: Genetic Variation Reed-Sternberg Cells MESH: DNA Mutational Analysis MESH : Immunoblotting MESH: Reed-Sternberg Cells Oncogene Proteins Genetics B-Lymphocytes 0303 health sciences Mutation MESH: Immunoblotting MESH : Oncogene Proteins NF-kappa B Hematology Transfection Hodgkin Disease MESH: Hodgkin Disease MESH : NF-kappa B 030220 oncology & carcinogenesis [SDV.IMM]Life Sciences [q-bio]/Immunology MESH : Mutation MESH : Transfection MESH: Mutation MESH : Recombinant Fusion Proteins Recombinant Fusion Proteins Immunoblotting Molecular Sequence Data MESH : Luciferases Renilla MESH : DNA Mutational Analysis Biology MESH: Sequence Homology Nucleic Acid MESH : B-Lymphocytes Cell Line Viral Matrix Proteins 03 medical and health sciences MESH: Oncogene Proteins stomatognathic system MESH : Genetic Variation Sequence Homology Nucleic Acid MESH: B-Lymphocytes medicine otorhinolaryngologic diseases MESH: Recombinant Fusion Proteins Animals Humans Hodgkin's Lymphoma MESH : Sequence Homology Nucleic Acid MESH: Tumor Cells Cultured Luciferases Renilla 030304 developmental biology MESH: Viral Matrix Proteins MESH: Molecular Sequence Data MESH: Humans MESH : Reed-Sternberg Cells Base Sequence MESH: Apoptosis MESH: Transfection MESH : Humans Genetic Variation medicine.disease Hodgkin's lymphoma Epstein–Barr virus Lymphoma MESH: Cell Line stomatognathic diseases Reed–Sternberg cell Cell culture Cancer research MESH : Base Sequence MESH : Animals Carcinogenesis MESH : Apoptosis |
| Zdroj: | Haematologica Haematologica, Ferrata Storti Foundation, 2009, 94 (3), pp.355-63. ⟨10.3324/haematol.13269⟩ Haematologica, Ferrata Storti Foundation, 2009, 94 (3), pp.355-63. 〈10.3324/haematol.13269〉 |
| ISSN: | 0390-6078 1592-8721 |
| DOI: | 10.3324/haematol.13269⟩ |
| Popis: | International audience; BACKGROUND: In Epstein-Barr virus-associated Hodgkin's lymphomas, neoplastic Reed-Sternberg cells and surrounding non-tumor B-cells contain different variants of the LMP1-BNLF1 oncogene. In this study, we raised the question of functional properties of latent membrane protein 1 (LMP1) natural variants from both Reed-Sternberg and non-tumor B-cells. DESIGN AND METHODS: Twelve LMP1 natural variants from Reed-Sternberg cells, non-tumor B-cells of Hodgkin's lymphomas and from B-cells of benign reactive lymph nodes were cloned, sequenced and stably transfected in murine recombinant interleukin-3-dependent Ba/F3 cells to search for relationships between LMP1 cellular origin and oncogenic properties as well as nuclear factor-kappaB activation, and apoptosis protection. RESULTS: LMP1 variants of Reed-Sternberg cell origin were often associated with increased mutation rate and with recurrent genetic events, such as del15bp associated with S to N replacement at codon 309, and four substitutions I85L, F106Y, I122L, and M129I. Oncogenic potential (growth factor-independence plus clonogenicity) was consistently associated with LMP1 variants from Reed-Sternberg cells, but inconstantly for LMP1-variants from non-tumor B-cells. Analysis of LMP1 variants from both normal B-cells and Reed-Sternberg cells indicates that protection against apoptosis through activation of nuclear factor-kappaB - whatever the cellular origin of LMP1 - was maintained intact, regardless of the mutational pattern. CONCLUSIONS: Taken together, our results demonstrate that preserved nuclear factor-kappaB activity and protection against apoptosis would be the minimal prerequisites for all LMP1 natural variants from both normal and tumor cells in Hodgkin's lymphomas, and that oncogenic potential would constitute an additional feature for LMP1 natural variants in Reed-Sternberg cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|