Upregulation of cyclooxygenase-2 is accompanied by increased expression of nuclear factor-kappa B and I kappa B kinase-alpha in human colorectal cancer epithelial cells.
Upregulation of cyclooxygenase-2 is accompanied by increased expression of nuclear factor-kappa B and I kappa B kinase-alpha in human colorectal cancer epithelial cells.
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DOI：
10.1038/sj.bjc.6600927
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发表时间：
2003-05-19
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
环氧合酶-2(COX-2)在结直肠肿瘤中选择性过表达。COX-2的诱导机制尚不完全清楚，但需要从头信使RNA和蛋白质的合成，表明在转录水平上的调控。COX-2基因5‘侧翼区的序列分析显示有两个核因子-κB(核因子-κB)位点。在模型细胞培养系统中抑制该蛋白可减弱COX-2的表达，并暗示NF-κB在COX-2诱导过程中起重要作用。应用免疫组织化学方法检测32例结直肠癌患者的结肠活检标本中COX-2、核因子-κB和I-κB激酶α(IKKα)蛋白的表达。COX-2、NF-κB和IKKα在非肿瘤性结肠上皮细胞中无表达或仅有极少量表达，而癌旁组织中这三种蛋白的表达均显著增强(P<；0.05，Wilcoxon‘s Signed RANK检验)。此外，还发现这三种蛋白在肿瘤上皮细胞中均有共同表达，且COX-2和NF-κB的表达高度相关(皮尔逊相关性，P<；0.005)。COX-2、NF-κB、IKKα表达增强与肿瘤Dukes分期无明显相关性。我们的结果与IKKα和NF-κB参与这些肿瘤中COX-2诱导的假设是一致的，COX-2的表达与Dukes‘s分期的疾病严重程度之间缺乏相关性，这与COX-2的表达是早期的启动后事件的假设是一致的。
Cyclooxygenase-2 (COX-2) is selectively overexpressed in colorectal tumours. The mechanism of COX-2 induction is not fully understood, but requires de novo messenger RNA and protein synthesis, indicating regulation at the transcriptional level. Sequence analysis of the 5′-flanking region of the COX-2 gene shows two nuclear factor-κB (NF-κB) sites. Inhibition of this protein in model cell culture systems attenuates COX-2 expression and implies that NF-κB plays an important role in COX-2 induction. We measured COX-2, NF-κB and IκB kinase α (IKKα) protein expression in matched colonic biopsy samples comprising both nontumour and adjacent tumour tissue from 32 colorectal cancer patients using immunohistochemistry. There was none or very little expression of COX-2, NF-κB and IKKα in non-neoplastic colon epithelial cells, while the expression of all three of these proteins was significantly increased (P<0.05, Wilcoxon's signed rank test) in adjacent cancerous cells. Moreover, all three proteins were found to be coexpressed in the neoplastic epithelium, with the expression of COX-2 and NF-κB highly correlated (Pearson's correlation, P<0.005). There was no apparent correlation between enhanced COX-2, NF-κB or IKKα expression and tumour Dukes' stages. Our results are compatible with the hypothesis that IKKα and NF-κB are involved in COX-2 induction in these tumours and the lack of association between COX-2 expression and severity of disease as measured by Dukes' stage is consistent with the proposal that COX-2 expression is an early postinitiation event.
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影响因子：
11.4
作者：
PAHL, HL;BAEUERLE, PA
通讯作者：
BAEUERLE, PA
影响因子：
4.4
作者：
Chen, CC;Sun, YT;Chiu, KT
通讯作者：
Chiu, KT
DOI：
10.1073/pnas.86.7.2336
发表时间：
1989-04-01
影响因子：
11.1
作者：
OSBORN, L;KUNKEL, S;NABEL, GJ
通讯作者：
NABEL, GJ
DOI：
10.1073/pnas.92.18.8458
发表时间：
1995-08-29
影响因子：
11.1
作者：
JANSSEN, YMW;BARCHOWSKY, A;MOSSMAN, BT
通讯作者：
MOSSMAN, BT
DOI：
10.1084/jem.184.3.883
发表时间：
1996-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Portanova JP;Zhang Y;Anderson GD;Hauser SD;Masferrer JL;Seibert K;Gregory SA;Isakson PC
通讯作者：
Isakson PC