Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours.
Biallelic NF2 gene inactivation is frequently found in human malignant mesothelioma. In order to assess whether NF2 hemizygosity may enhance susceptibility to asbestos fibres, we investigated the Nf2 status in mesothelioma developed in mice presenting a heterozygous mutation of the Nf2 gene (Nf2(KO3/+)), after intraperitoneal inoculation of crocidolite fibres. Asbestos-exposed Nf2(KO3/+) mice developed tumoural ascites and mesothelioma at a higher frequency than their wild-type (WT) counterparts (P&<0.05). Six out of seven mesothelioma cell lines established from neoplastic ascitic fluids of Nf2(KO3/+) mice exhibited loss of the WT Nf2 allele and no neurofibromatosis type 2 protein expression was found in these cells. The results show the importance of the NF2 gene in mesothelial oncogenesis, the potential association of asbestos exposure and tumour suppressor gene inactivation, and suggest that NF2 gene mutation may be a susceptibility factor to asbestos.
Fleury-Feith
Jocelyne
J
INSERM EMI 99.09, Université Paris XII, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil, France.
Lecomte
Céline
C
Renier
Annie
A
Matrat
Mireille
M
Kheuang
Laurence
L
Abramowski
Vincent
V
Levy
Françoise
F
Janin
Anne
A
Giovannini
Marco
M
Jaurand
Marie-Claude
MC
D000818:Animals; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D016515:Genes, Neurofibromatosis 2; D020022:Genetic Predisposition to Disease; D008654:Mesothelioma / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017638:Asbestos, Crocidolite