Microsatellite instability and protein expression of the DNA mismatch repair gene, hMLH1, of lung cancer in chromate-exposed workers
Microsatellite instability and protein expression of the DNA mismatch repair gene, hMLH1, of lung cancer in chromate-exposed workers
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DOI：
10.1002/mc.20073
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发表时间：
2005-03-01
影响因子：
4.6
通讯作者：
Monden, Y
中科院分区：
文献类型：
--
作者：
Takahashi, Y;Kondo, K;Monden, Y
我们之前对铬酸盐暴露工人肺癌（铬酸盐肺癌）的研究表明，铬酸盐肺癌的复制错误（RER）频率非常高。我们研究了铬酸盐肺癌的RER表型是否由于DNA错配修复蛋白的异常。我们利用免疫组织化学和微卫星不稳定性（MSI）研究了DNA错配修复基因hMLH1和hMSH2蛋白在35例铬酸盐肺癌和26例非铬酸盐肺癌中的表达。没有MSI或在一个位点有MSI的肺癌被定义为“RER（-）”，两个位点有MSI的肺癌被定义为“RER（+）”，三个或更多位点有MSI的肺癌被定义为“RER（++）”。hMLH1和hMSH2蛋白在铬酸盐肺癌中的抑制率明显高于非铬酸盐肺癌（hMLH1: 56% vs. 20%, P = 0.006, hMSH2: 74% vs. 23%, P < 0.0001）。在铬酸盐肺癌中，hMLH1在RER（-）组的抑制率为43%，在RER（+）组的抑制率为40%，在RER（++）组的抑制率为90%。hMLH1蛋白在RER（++）组的抑制率显著高于RER（-）和RER（+）组（P = 0.039）， hMLH1表达失活与铬酸盐肺癌的微卫星高不稳定性表型密切相关。铬酸盐肺癌的遗传不稳定性是由于hMLH1蛋白的抑制。(C) 2004 Wiley-Liss, Inc。
Our previous studies of lung cancer in chromate-exposed workers (chromate lung cancer) have revealed that the frequency of replication error (RER) in chromate lung cancer is very high. We examined whether the RER phenotype of chromate lung cancer is due to an abnormality of DNA mismatch repair protein. We investigated the expression of a DNA mismatch repair gene, hMLH1, and hMSH2 proteins using immunohistochemistry and microsatellite instability (MSI) in 35 chromate lung cancers and 26 nonchromate lung cancers. Lung cancer without MSI or with MSI at one locus was defined as "RER(-)," lung cancer with MSI at two loci was defined as "RER(+)," and lung cancer with MSI at three or more loci was defined as "RER(++)." The repression rate of hMLH1 and hMSH2 proteins in chromate lung cancer was significantly more than that of nonchromate lung cancer (hMLH1: 56% vs. 20%, P = 0.006, hMSH2: 74% vs, 23%, P < 0.0001). in chromate lung cancer, the repression rate for hMLH1 was 43% in RER(-), 40% in RER(+), and 90% in the RER(++) group. The repression rate of hMLH1 protein in the RER(++) group was significantly higher than that in the RER(-) and RER(+) groups (P = 0.039), The inactivation of hMLH1 expression strongly correlated with the microsatellite high instability phenotype in chromate lung cancer. The genetic instability of chromate lung cancer is due to the repression of hMLH1 protein. (C) 2004 Wiley-Liss, Inc.