Tumour suppressor PTEN enhanced enzyme activity of GPx, SOD and catalase by suppression of PI3K/AKT pathway in non-small cell lung cancer cell lines
Tumour suppressor PTEN enhanced enzyme activity of GPx, SOD and catalase by suppression of PI3K/AKT pathway in non-small cell lung cancer cell lines
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DOI：
10.3109/14756366.2011.654114
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发表时间：
2013-06-01
影响因子：
5.6
通讯作者：
Tokgun, Onur
中科院分区：
文献类型：
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作者：
Akca, Hakan;Demiray, Aydin;Tokgun, Onur
10号染色体上缺失的磷酸盐和张力蛋白同源物（PTEN）是一种肿瘤抑制基因，其使磷酸肌醇3，4，5三磷酸去磷酸化。因此，PTEN可以调节细胞中的PI3K/AKT通路。由于启动子甲基化或基因缺失，非小细胞肺癌（NSCLC）细胞系中PTEN表达通常降低或缺失。因此，我们推测PTEN可以调节超氧化物歧化酶（CuZnSOD），谷胱甘肽过氧化物酶（GPx）和过氧化氢酶的活性。我们首先在肺细胞系中重建了PTENwt、G129R和G129E表达，其中未检测到内源性PTEN表达。然后，我们发现PTEN可以通过其脂质磷酸酶结构域抑制AKT活性。然后，我们检查了重建的PTEN表达在NSCLC细胞中的作用。而PTENwt的表达引起的SOD，GPx和过氧化氢酶在转染细胞系的活性增强，无论是G129 R或G129 E的表达影响酶的活性。提示PTEN可通过抑制PI3K/AKT通路上调NSCLC细胞SOD、GPx和CAT活性。
Phosphates and tensin homologue deleted on chromosome 10 (PTEN) is a tumour suppressor gene which dephosphorilates phosphoinositol 3,4,5 triphosphates. Therefore PTEN can regulate PI3K/AKT pathway in cells. Because of promoter methylation or gene deletion, PTEN expression is commonly decreased or lost in non-small cell lung cancer (NSCLC) cell lines. Therefore, we hypothesized that PTEN could regulate the activity of superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx) and catalase. We first recreated PTENwt, G129R and G129E expressions in lung cell lines, in which endogenous PTEN expression was not detected. Then, we showed that PTEN could suppress AKT activity by its lipid phosphatase domain. We then examined the effect of recreated PTEN expressions in NSCLC cells. While PTENwt expression caused enhanced activity of SOD, GPx and catalase in transfected cells lines, neither G129R nor G129E expression effected enzyme activities. These results suggest that PTEN can up-regulate SOD, GPx and catalase activity by inhibition of PI3K/AKT pathway in NSCLC cell lines.