Loss of glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma.
Loss of glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma.
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DOI：
10.1186/1475-2867-10-46
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发表时间：
2010-11-24
影响因子：
5.8
通讯作者：
Klinga-Levan K
中科院分区：
文献类型：
--
作者：
Falck E;Karlsson S;Carlsson J;Helenius G;Karlsson M;Klinga-Levan K
谷胱甘肽过氧化物酶3（GPX 3）是细胞防御氧化应激的关键酶之一，肝细胞生长因子受体（MET）被认为受到GPX 3基因表达的影响。在我们小组先前进行的微阵列研究中，Gpx 3被鉴定为大鼠子宫内膜腺癌（EAC）的潜在生物标志物，因为其表达在大鼠EAC肿瘤中高度下调。本研究采用真实的时间定量PCR（qPCR）技术检测大鼠EAC中Gpx 3和Met的mRNA表达，并检测Gpx 3的甲基化状态。此外，我们还检测了GPX 3和MET在30例不同FIGO分级的人EAC和20例良性子宫内膜组织中的表达。我们发现GPX 3的表达在大鼠和人EAC中均一致下调，无论肿瘤分级或组织病理学亚型如何，这意味着下调是EAC的早期事件。Gpx 3启动子甲基化率达到91%，其中90%的甲基化肿瘤中存在双等位基因甲基化。Met癌基因的表达在Gpx 3表达缺失的EAC中略微上调，但未检测到Gpx 3/GPX 3的肿瘤抑制活性。初步结果还表明，在Gpx 3表达下调的大鼠子宫内膜肿瘤中，H2 O2的产生更高。GPX 3蛋白功能丧失的一个可能后果是癌细胞环境中的ROS量更高。因此，结果表明EAC中GPX 3表达的重要临床意义，既作为EAC的分子生物标志物，又作为治疗干预的潜在靶点。
Glutathione peroxidase 3 (GPX3) is one of the key enzymes in the cellular defense against oxidative stress and the hepatocyte growth factor receptor, (MET) has been suggested to be influenced by the GPX3 gene expression. In a previous microarray study performed by our group, Gpx3 was identified as a potential biomarker for rat endometrial adenocarcinoma (EAC), since the expression was highly downregulated in rat EAC tumors. Herein, we have investigated the mRNA expression and Gpx3 and Met in rat EAC by real time quantitative PCR (qPCR), and the methylation status of Gpx3. In addition we have examined the expression of GPX3 and MET in 30 human EACs of different FIGO grades and 20 benign endometrial tissues. We found that the expression of GPX3 was uniformly down regulated in both rat and human EAC, regardless of tumor grade or histopathological subtype, implying that the down-regulation is an early event in EAC. The rate of Gpx3 promoter methylation reaches 91%, where biallelic methylation was present in 90% of the methylated tumors. The expression of the Met oncogene was slightly upregulated in EACs that showed loss of expression of Gpx3, but no tumor suppressor activity of Gpx3/GPX3 was detected. Preliminary results also suggest that the production of H2O2 is higher in rat endometrial tumors with down-regulated Gpx3 expression. A likely consequence of loss of GPX3 protein function would be a higher amount of ROS in the cancer cell environment. Thus, the results suggest important clinical implications of the GPX3 expression in EAC, both as a molecular biomarker for EAC and as a potential target for therapeutic interventions.
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影响因子：
4.8
作者：
Lee, OJ;Schneider-Stock, R;El-Rifai, W
通讯作者：
El-Rifai, W
DOI：
10.1073/pnas.94.2.701
发表时间：
1997-01-21
影响因子：
11.1
作者：
Takayama, H;LaRochelle, WJ;Merlino, G
通讯作者：
Merlino, G
通过细胞附着激活 Met 受体可诱导并维持转基因小鼠的肝细胞癌。
影响因子：
7.8
作者：
Wang, R;Ferrell, DL;Faouzi, S;Maher, JJ;Bishop, JM
通讯作者：
Bishop, JM
影响因子：
56.9
作者：
BOTTARO, DP;RUBIN, JS;AARONSON, SA
通讯作者：
AARONSON, SA
影响因子：
11.2
作者：
Taulli, Riccardo;Scuoppo, Claudio;Ponzetto, Carola
通讯作者：
Ponzetto, Carola