Nf2基因半合子状态与石棉诱导的腹膜肿瘤易感性增加有关。

Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours.

作者信息

Fleury-Feith Jocelyne, Lecomte Céline, Renier Annie, Matrat Mireille, Kheuang Laurence, Abramowski Vincent, Levy Françoise, Janin Anne, Giovannini Marco, Jaurand Marie-Claude

机构信息

INSERM EMI 99.09, Université Paris XII, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil, France.

出版信息

Oncogene. 2003 Jun 12;22(24):3799-805. doi: 10.1038/sj.onc.1206593.

DOI:10.1038/sj.onc.1206593

PMID:12802287

Abstract

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.

摘要

双等位基因NF2基因失活在人类恶性间皮瘤中经常被发现。为了评估NF2半合子状态是否会增加对石棉纤维的易感性，我们在腹腔接种青石棉纤维后，研究了携带Nf2基因杂合突变（Nf2(KO3/+)）的小鼠发生的间皮瘤中的Nf2状态。接触石棉的Nf2(KO3/+)小鼠发生肿瘤性腹水和间皮瘤的频率高于其野生型（WT）对照（P＜0.05）。从Nf2(KO3/+)小鼠的肿瘤性腹水中建立的七个间皮瘤细胞系中有六个显示野生型Nf2等位基因缺失，并且在这些细胞中未发现2型神经纤维瘤蛋白表达。结果表明NF2基因在间皮瘤发生中的重要性、石棉暴露与肿瘤抑制基因失活的潜在关联，并提示NF2基因突变可能是对石棉的易感因素。