Clinico-pathological features and somatic gene alterations in refractory ceramic fibre-induced murine mesothelioma reveal mineral fibre-induced mesothelioma identities

Autor: Andujar, Pascal, Lecomte, Céline, Renier, Annie, Fleury-Feith, Jocelyne, Kheuang, Laurence, Daubriac, Julien, Janin, Anne, Jaurand, Marie-Claude
Přispěvatelé: Institut Mondor de recherche biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Laboratoire d'histologie et de biologie tumorale, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Service de pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Ministère de l'Environnement n°AC008B, Ministère de l'Emploi et de la Solidarité n°1D004C, Ligue Nationale contre le Cancer, Cancéropôle Ile-de-France and Legs Poix, Association de la Recherche contre le Cancer, Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Mesothelioma
MESH : Mesothelioma
INK4
[SDV.CAN]Life Sciences [q-bio]/Cancer
MESH : Ceramics
Tumour suppressor genes
MESH : Cyclin-Dependent Kinase Inhibitor Proteins
MESH: Mice
Knockout
MESH: Mineral Fibers
[ SDV.CAN ] Life Sciences [q-bio]/Cancer
MESH: Ceramics
MESH : Cells
Cultured
MESH : Mice
otorhinolaryngologic diseases
MESH : Mineral Fibers
MESH: Animals
MESH: Ascites
MESH: Tumor Suppressor Protein p53
MESH: Cyclin-Dependent Kinase Inhibitor Proteins
MESH: Mice
MESH : Neurofibromin 2
MESH: Mesothelioma
Cell Cycle
MESH: Neurofibromin 2
MESH : Cyclin-Dependent Kinase Inhibitor p16
MESH : Disease Models
Animal
MESH : Tumor Suppressor Protein p53
Knockout-mice
MESH: Cyclin-Dependent Kinase Inhibitor p16
NF2
MESH : Ascites
MESH : Mice
Knockout
MESH : Animals
MESH: Disease Models
Animal
Ceramic fibres
MESH: Cells
Cultured
Zdroj: Carcinogenesis / CARCINOGENESIS(LONDON); Carcinogenesis (Oxford)
Carcinogenesis / CARCINOGENESIS(LONDON); Carcinogenesis (Oxford), 2007, 28 (7), pp.1599-605. 〈10.1093/carcin/bgm023〉
Carcinogenesis / CARCINOGENESIS(LONDON); Carcinogenesis (Oxford), 2007, 28 (7), pp.1599-605. ⟨10.1093/carcin/bgm023⟩
DOI: 10.1093/carcin/bgm023〉
Popis: International audience; Although human malignant mesothelioma (HMM) is mainly caused by asbestos exposure, refractory ceramic fibres (RCFs) have been classified as possibly carcinogenic to humans on the basis of their biological effects in rodents' lung and pleura and in cultured cells. Hence, further investigations are needed to clarify the mechanism of fibre-induced carcinogenicity and to prevent use of harmful particles. In a previous study, mesotheliomas were found in hemizygous Nf2 (Nf2(+/-)) mice exposed to asbestos fibres, and showed similar alterations in genes at the Ink4 locus and in Trp53 as described in HMM. Here we found that Nf2(+/-) mice developed mesotheliomas after intra-peritoneal inoculation of a RCF sample (RCF1). Clinical features in exposed mice were similar to those observed in HMM, showing association between ascite and mesothelioma. Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2(+/-) mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations. Nf2 gene was inactivated in all cultures. In most cases, co-inactivation of genes at the Ink4 locus and Nf2 was found and, at a lower rate, of Trp53 and Nf2. These results are the first to identify mutations in RCF-induced mesothelioma. They suggest that nf2 mutation is complementary of p15(Ink4b), p16(Ink4a) and p19(Arf) or p53 mutations and show similar profile of gene alterations resulting from exposure to ceramic or asbestos fibres in Nf2(+/-) mice, also consistent with the one found in HMM. These somatic genetic changes define different pathways of mesothelial cell transformation.
Databáze: OpenAIRE
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