Increased noxl and hydrogen peroxide in prostate cancer

Increased noxl and hydrogen peroxide in prostate cancer
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DOI:
10.1002/pros.20137
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发表时间:
2005-02-01
期刊:
影响因子:
2.8
通讯作者:
Arnold, RS
Arnold, RS
中科院分区:
医学3区
文献类型:
--
作者:
Lim, SD;Sun, C;Arnold, RS

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背景。活性氧(ROS)正在成为癌症生长和血管生成的候选介质。 ROS 增加通常与细胞生长相关,例如 Ras 转化细胞和用生长因子处理的细胞。虽然非转化细胞通过调节 ROS 的产生来响应生长因子/细胞因子,但培养中的肿瘤细胞经常过量产生 H2O2。我们认为 NADPH 氧化酶 (Nox) 是某些癌症中 ROS 水平升高的原因。此前,将Nox1转染至前列腺癌细胞系中可显着增强肿瘤生长(Arbiser等人:PNAS 99:715-720,2001)。利用免疫组织化学、免疫荧光、二氢乙锭染色和流式细胞术,我们研究了前列腺癌中Nox1和ROS之间的相关性。结果。在这里,我们证明人类前列腺肿瘤的 H2O2 水平升高。此外,80% 的人类前列腺肿瘤样本显示 Nox1 蛋白水平和 mRNA 水平显着增加。此外,由 LNCaP 前列腺癌细胞开发的一系列细胞系显示肿瘤和转移潜力增加,Nox1 增加,H2O2 水平平行增加。结论。结果表明,人类前列腺癌经常表现出 H2O2 和 Nox1 增加,并且在动物模型系统中,Nox1/H2O2 增加与致瘤性增加相关。 (C) 2004 Wiley-Liss, Inc.
BACKGROUND. Reactive oxygen species (ROS) are emerging as candidate mediators of growth and angiogenesis in cancer. Increased ROS often correlates with cell growth, e.g., Ras-transformed cells and cells treated with growth factors. While non-transformed cells respond to growth factors/cytokines with the regulated production of ROS, tumor cells in culture frequently overproduce H2O2. We propose that NADPH oxidases (Nox) account for increased levels of ROS in some cancers. Previously, transfection of Nox1 into a prostate cancer cell line dramatically enhanced tumor growth (Arbiser et al.: PNAS 99:715-720, 2001).METHODS. Using immunohistochemistry, immunofluorescence, dihydroethidium staining, and Flow cytometry, we investigated the correlation between Nox1 and ROS in prostate cancer.RESULTS. Here, we demonstrate that human prostate tumors show increased H2O2 levels. Furthermore, 80% of human prostate tumor samples show markedly increased Nox1 protein levels and increased mRNA levels. In addition, a series of cell lines developed from LNCaP prostate cancer cells that demonstrate increasing tumor and metastatic potential, show increased Nox1 and a parallel increase in H2O2 levels.CONCLUSIONS. The results illustrate that human prostate cancer frequently show both increased H2O2 and Nox1, and that in an animal model system increased Nox1/H2O2 correlates with increased tumorigenicity. (C) 2004 Wiley-Liss, Inc.