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首页> 外文期刊>Molecular Carcinogenesis >Microsatellite instability and protein expression of the DNA mismatch repair gene, hMLH1, of lung cancer in chromate-exposed workers.
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Microsatellite instability and protein expression of the DNA mismatch repair gene, hMLH1, of lung cancer in chromate-exposed workers.

机译:铬酸盐暴露工人肺癌DNA错配修复基因hMLH1的微卫星不稳定性和蛋白质表达。

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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(+), RER(++). 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.
机译:我们先前对铬酸盐暴露工人的肺癌研究(铬酸盐肺癌)表明,铬酸盐肺癌的复制错误(RER)频率很高。我们检查了铬酸盐肺癌的RER表型是否是由于DNA错配修复蛋白的异常引起的。我们调查了35种铬酸盐肺癌和26种非铬酸盐肺癌中使用免疫组织化学和微卫星不稳定性(MSI)的DNA错配修复基因,hMLH1和hMSH2蛋白的表达。没有MSI或在一个位点有MSI的肺癌定义为“ RER(-)”,在两个位点有MSI的肺癌定义为RER(+),RER(++)。肺癌的发生率明显高于非铬酸盐肺癌(hMLH1:56%比20%,P = 0.006,hMSH2:74%比23%,P <0.0001)。在铬酸盐肺癌中,hMLH1的抑制率在RER(-)组为43%,在RER(+)组为40%,在RER(++)组为90%。 RER(++)组中hMLH1蛋白的抑制率显着高于RER(-)和RER(+)组(P = 0.039)。 hMLH1表达的失活与铬酸盐肺癌中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蛋白的抑制所致。

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