Nox1 is over-expressed in human colon cancers and correlates with activating mutations in K-Ras.
Nox1 is over-expressed in human colon cancers and correlates with activating mutations in K-Ras.
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DOI：
10.1002/ijc.23423
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发表时间：
2008-07-01
影响因子：
6.4
通讯作者：
Lambeth, J. David
中科院分区：
文献类型：
--
作者：
Laurent, Eunice;McCoy, James W., III;Macina, Roberto A.;Liu, Wenhui;Cheng, Guangjie;Robine, Sylvie;Papkoff, Jackie;Lambeth, J. David
NADPH氧化酶1（Nox 1）是gp 91 phox的同源物，gp 91 phox是吞噬细胞产生超氧化物的NADPH氧化酶的催化亚基。Nox 1在正常结肠上皮细胞和结肠肿瘤细胞系中表达，并且在模型细胞中的过表达已经涉及刺激有丝分裂和血管生成以及抑制细胞凋亡。这表明Nox 1的异常表达可能有助于结直肠癌的发展。在此，我们研究了Nox 1 mRNA在24个不同阶段的结肠肿瘤中的表达，并与来自同一患者的配对相邻正常组织进行比较，并将表达与结肠癌相关的一些常见突变相关联。早在腺瘤阶段，57%的肿瘤中Nox 1与配对的正常组织相比过表达，表达水平与肿瘤分期无关。通过免疫荧光和免疫组织化学方法用Nox 1特异性抗体评估Nox 1 mRNA的过表达与Nox 1蛋白水平相关。Nox 1 mRNA水平与K-Ras第12和13密码子激活突变密切相关。80%（8/10）的密码子12和13突变的肿瘤中Nox 1 mRNA增加2倍或更多，70%（7/10）增加5倍或更多。在肠上皮中表达K-RasG 12 V的转基因小鼠在小肠和大肠中也表达显著升高的Nox 1。肿瘤抑制基因p53的失活突变与Nox 1的表达无相关性。我们的结论是，Nox 1 mRNA和蛋白在结肠癌中过表达，并与K-Ras的激活突变密切相关。
The NADPH-oxidase 1 (Nox1) is a homolog of gp91phox, the catalytic subunit of the phagocyte superoxide-generating NADPH-oxidase. Nox1 is expressed in normal colon epithelial cells and in colon tumor cell lines, and overexpression in model cells has been implicated in stimulation of mitogenesis and angiogenesis and inhibition of apoptosis. This suggests that aberrant expression of Nox1 could contribute to the development of colorectal cancer. Herein, we examine the expression of Nox1 mRNA in 24 colon tumors of various stages compared with paired adjacent normal tissue from the same patient, and correlate expression with some common mutations associated with colon cancer. Nox1 was overexpressed compared with paired normal tissue in 57% of tumors as early as the adenoma stage, with no correlation of expression level with tumor stage. Overexpression of Nox1 mRNA correlated with Nox1 protein levels assessed by immunofluorescence and immunohistochemistry with an antibody specific for Nox1. There was a strong correlation between Nox1 mRNA level and activating mutations in codons 12 and 13 of K-Ras. Eighty percent (8/10) of tumors with codons 12 and 13 mutations had a 2-fold or more increase in Nox1 mRNA, and 70% (7/10) had a 5-fold or greater increase. Transgenic mice expressing K-RasG12V in the intestinal epithelium also expressed markedly elevated Nox1 in both small and large intestine. There was no correlation between inactivating mutations in the tumor suppressor p53 and Nox1 expression. We conclude that Nox1 mRNA and protein are overexpressed in colon cancer and are strongly correlated with activating mutations in K-Ras.
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影响因子：
4.8
作者：
Cheng, Guangjie;Diebold, Becky A.;Lambeth, J. David
通讯作者：
Lambeth, J. David
影响因子：
4.4
作者：
Geiszt, M;Lekstrom, K;Leto, TL
通讯作者：
Leto, TL
影响因子：
--
作者：
Bartsch, H;Nair, J
通讯作者：
Nair, J
影响因子：
4.8
作者：
Joneson, T;Bar-Sagi, D
通讯作者：
Bar-Sagi, D
影响因子：
5.5
作者：
Brar, SS;Kennedy, TP;Hoidal, JR
通讯作者：
Hoidal, JR