Nox1 expression determines cellular reactive oxygen and modulates c-fos-induced growth factor, interleukin-8, and Cav-1
Nox1 expression determines cellular reactive oxygen and modulates c-fos-induced growth factor, interleukin-8, and Cav-1
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DOI：
10.2353/ajpath.2007.061144
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发表时间：
2007-12-01
影响因子：
6
通讯作者：
Petros, John A.
中科院分区：
文献类型：
--
作者：
Arnold, Rebecca S.;He, Ju;Petros, John A.
增加的细胞活性氧物质（ROS）除了破坏DNA和氧化脂质和蛋白质之外，还可以作为促有丝分裂信号，这暗示ROS参与癌症的发展和进展。为了分析Nox 1表达的影响及其与细胞ROS和参与细胞增殖的信号转导的关系，将Nox 1 RNAi构建体转染到过表达Nox 1的DU 145前列腺癌细胞中，导致Nox 1 RNAi细胞系中Nox 1信息和蛋白水平降低。在Nox 1 RNAi的存在下，Nox 1过表达的DU 145细胞中增加的ROS和肿瘤生长被逆转。在过表达和RNAi细胞中的信息水平的分析和比较表明，Nox 1过表达导致包括c-fos诱导的生长因子、白细胞介素-8和Cav-1在内的多种蛋白质的信息水平的变化。最后，我们发现，Nox 1蛋白过表达是一个早期事件，在前列腺癌的发展，使用国家癌症研究所前列腺癌组织微阵列（CPCTR）。肿瘤（86%）比良性前列腺组织（62%）更可能具有Nox 1染色（P = 0.0001）。这些研究表明，Nox 1过表达可能作为一个可逆的信号细胞增殖与相关的一个共同的人类肿瘤。
increased cellular reactive oxygen species (ROS) can act as mitogenic signals in addition to damaging DNA and oxidizing lipids and proteins, implicating ROS in cancer development and progression. To analyze the effects of Nox1 expression and its relation to cellular ROS and signal transduction involved in cellular proliferation, Nox1RNAi constructs were transfected into DU145 prostate cancer cells overexpressing Nox1, causing decreased Nox1 message and protein levels in the Nox1RNAi cell lines. Increased ROS and tumor growth in the Nox1-overexpressing DU145 cells were reversed in the presence of the Nox1RNAi. Analysis and comparison of the message levels in the overexpression and RNAi cells demonstrated that Nox1 overexpression leads to changes in message levels of a variety of proteins including c-fos-induced growth factor, interleukin-8, and Cav-1. Finally, we found that Nox1 protein overexpression is an early event in the development of prostate cancer using a National Cancer Institute prostate cancer tissue microarray (CPCTR). Tumor (86%) was significantly more likely to have Nox1 staining than benign prostate tissue (62%) (P = 0.0001). These studies indicate that Nox1 overexpression may function as a reversible signal for cellular proliferation with relevance for a common human tumor.