Accumulation of hRad9 protein in the nuclei of nonsmall cell lung carcinoma cells
Accumulation of hRad9 protein in the nuclei of nonsmall cell lung carcinoma cells
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DOI：
10.1002/cncr.20740
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发表时间：
2005-01-01
期刊：
影响因子：
6.2
通讯作者：
Okita, Y
中科院分区：
文献类型：
--
作者：
Maniwa, Y;Yoshimura, M;Okita, Y
背景DNA损伤传感器蛋白作为DNA损伤检查点信号通路的上游成分而受到广泛关注，这些信号通路是细胞周期控制和诱导细胞凋亡所需的。这些蛋白质的缺陷与基因突变的积累直接相关，这些基因突变可诱导细胞转化并导致恶性疾病。采用免疫组化和Western blot方法，对48例手术切除的非小细胞肺癌（NSCLC）患者的肿瘤组织和周围正常肺组织中hRad 9蛋白的表达进行了研究。免疫组织化学分析检测到hRad 9在16个肿瘤组织标本的肿瘤细胞核中的积累，（33%的肿瘤组织标本检查）。蛋白质印迹分析还显示NSCLC细胞中磷酸化hRad 9蛋白水平升高，伴随着磷酸化Chk 1的检测，这是一种调节DNA损伤检查点途径下游信号传导的蛋白激酶。此外，hRad 9的强表达与所检测的Turner细胞中Ki-67表达指数的增加相关。本研究的结果提示Rad 9的表达可能在NSCLC细胞的细胞周期调控中起重要作用，并可能影响NSCLC细胞的表型。(C)2004年美国癌症协会。
BACKGROUND. DNA damage sensor proteins have received much attention as upstream components of the DNA damage checkpoint signaling pathway that are required for cell cycle control and the induction of apoptosis. Deficiencies in these proteins are directly linked to the accumulation of gene mutations, which call induce cellular transformation and result in malignant disease.METHODS. Using 48 sets of tumor tissue specimens and peripheral normal lung tissue specimens front 48 patients with nonsmall cell lung carcinoma (NSCLC) who underwent surgery, the authors investigated the expression of hRad9 protein, a member of the human DNA damage sensor family, using immunohistochemical and Western blot analyses.RESULTS. Immunohistochemical analysis detected the accumulation of hRad9 in the nuclei of tumor cells in 16 tumor tissue specimens, (33% of tumor tissue specimens examined). Western blot analysis also revealed elevated levels of phosphorylated hRad9 protein in NSCLC cells that was accompanied by the detection of phosphorylated Chk1, a protein kinase that regulates the downstream signaling of the DNA damage checkpoint pathway. Furthermore, strong expression of hRad9 was correlated with an increase in Ki-67 expression index in the turner cells that were examined.CONCLUSIONS. The findings made in the current study suggest that Rad9 expression may play an important role in cell cycle control in NSCLC cells and may influence NSCLC cell phenotype. (C) 2004 American Cancer Society.