Carbone Michele, Kratzke Robert A, Testa Joseph R
Cancer Immunology Program, Cardinal Bernardin Cancer Center, Department of Pathology, Loyola University Chicago, USA.
Semin Oncol. 2002 Feb;29(1):2-17. doi: 10.1053/sonc.2002.30227.
About 80% of malignant mesotheliomas (MM) in the Western World develop in individuals with higher than background exposure to asbestos. Only a fraction of those exposed to asbestos develop mesothelioma, indicating that additional factors play a role. Simian virus 40 (SV40), a DNA tumor virus that preferentially causes mesothelioma in hamsters, has been detected in several human mesotheliomas. The expression of the SV40 large tumor antigen in mesothelioma cells, and not in nearby stromal cells, and the capacity of antisense T-antigen treatment to arrest mesothelioma cell growth in vitro suggest that SV40 contributes to tumor development. The capacity of T-antigen to bind and inhibit cellular p53 and retinoblastoma (Rb)-family proteins in mesothelioma, together with the very high susceptibility of human mesothelial cells to SV40-mediated transformation in vitro, supports a causative role of SV40 in the pathogenesis of mesothelioma. Asbestos appears to increase SV40-mediated transformation of human mesothelial cells in vitro, suggesting that asbestos and SV40 may be cocarcinogens. p53 mutations are rarely found in mesothelioma; p16, p14ARF, and NF2 mutations/losses are frequent. Recent studies revealed the existence of a genetic factor that predisposes affected individuals to mesothelioma in the villages of Karain and Tuzkoy, in Anatolia, Turkey. Erionite, a type of zeolite, may be a cofactor in these same villages, where 50% of deaths are caused by mesothelioma. Mesothelioma appears to have a complex etiology in which environmental carcinogens (asbestos and erionite), ionizing radiation, viruses, and genetic factors act alone or in concert to cause malignancy.
在西方世界，约80%的恶性间皮瘤（MM）发生于石棉暴露水平高于背景值的个体。接触石棉的人群中只有一小部分会患上间皮瘤，这表明还有其他因素在起作用。猴病毒40（SV40）是一种DNA肿瘤病毒，在仓鼠中可优先诱发间皮瘤，在多例人类间皮瘤中也检测到了该病毒。SV40大T抗原在间皮瘤细胞而非邻近基质细胞中表达，且反义T抗原治疗能在体外抑制间皮瘤细胞生长，这表明SV40参与了肿瘤的发生发展。T抗原在间皮瘤中能够结合并抑制细胞中的p53和视网膜母细胞瘤（Rb）家族蛋白，同时人胸膜间皮细胞在体外对SV40介导的转化具有极高的敏感性，这些都支持了SV40在间皮瘤发病机制中具有致病作用。石棉在体外似乎会增加SV40介导的人胸膜间皮细胞转化，这表明石棉和SV40可能是协同致癌物。间皮瘤中很少发现p53突变；p16、p14ARF和NF2突变/缺失则较为常见。最近的研究表明，在土耳其安纳托利亚的卡兰村和图兹科伊村，存在一种使受影响个体易患间皮瘤的遗传因素。毛沸石是一种沸石，在这些村庄可能是一种辅助因素，当地50%的死亡由间皮瘤导致。间皮瘤的病因似乎很复杂，环境致癌物（石棉和毛沸石）、电离辐射、病毒和遗传因素单独或共同作用导致恶性肿瘤的发生。
