Decreased carbonyl reductase 1 expression promotes malignant behaviours by induction of epithelial mesenchymal transition and its clinical significance
Decreased carbonyl reductase 1 expression promotes malignant behaviours by induction of epithelial mesenchymal transition and its clinical significance
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DOI：
10.1016/j.canlet.2012.03.035
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发表时间：
2012-10-01
期刊：
影响因子：
9.7
通讯作者：
Sugino, Norihiro
中科院分区：
文献类型：
--
作者：
Murakami, Akihiro;Yakabe, Kazuyuki;Sugino, Norihiro
人羰基还原酶1（CBR 1）是一种利用NADPH依赖性氧化还原酶活性催化许多化合物还原的酶。虽然已知CBR 1调节肿瘤进展，但CBR 1在癌症进展中的分子机制以及CBR 1状态的临床意义仍不清楚。在这里，我们研究了CBR 1影响癌细胞体外行为的分子机制，以及在子宫内膜癌中使用免疫组织化学分析CBR 1的临床意义。本研究通过将CBR 1的正义和反义cDNA转染人子宫内膜腺癌细胞系，研究CBR 1在癌细胞侵袭和转移中的作用及其分子机制。在来自FIGO I-IV期（n = 109）的子宫内膜癌组织中检查通过免疫组织化学分析的CBR 1表达与预后如无进展生存期（PFS）和总生存期（OS）之间的关系。通过反义CBR 1 cDNA抑制CBR 1增加癌细胞侵袭，并抑制E-钙粘蛋白表达和细胞聚集能力。相反，正义CBR 1 cDNA过表达CBR 1增加E-钙粘蛋白表达和细胞聚集能力，并抑制癌细胞侵袭。E-cadherin的转录抑制因子Snail和ZEB 1的表达被CBR 1抑制而增加，但被CBR 1过表达抑制。免疫组化分析显示，与强CBR 1表达相比，CBR 1表达降低与PFS和OS差显著相关。在多变量分析中，CBR 1表达降低是PFS和OS的独立预后因素。CBR 1通过调节上皮间质转化来调节子宫内膜腺癌中的癌细胞侵袭。CBR 1表达降低可能是子宫内膜癌患者不利临床结局的有用标志。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Human carbonyl reductase 1 (CBR1) is an enzyme that catalyse the reduction of many compounds by using NADPH-dependent oxydoreductase activity. Although CBR1 is known to regulate the tumour progression, the molecular mechanisms of CBR1 in cancer progression and the clinical significance of CBR1 status remain unclear. Here, we investigated the molecular mechanisms by which CBR1 affects cancer cell behaviour in vitro and the clinical significance of CBR1 using immunohistochemical analyses in endometrial cancer. Here, the role of CBR1 in cancer cell invasion and metastasis, and its molecular mechanisms were investigated by transfection of sense and antisense CBR1 cDNAs into a human endometrial adenocarcinoma cell line. The relationship between CBR1 expression analysed by immunohistochemistry and prognosis such as progression free survival (PFS) and overall survival (OS) was examined in endometrial cancer tissues from FIGO stage I-IV (n = 109). Suppression of CBR1 by antisense CBR1 cDNA increased cancer cell invasion, and suppressed E-cadherin expression and capacity for cellular aggregation. In contrast, over-expression of CBR1 by sense CBR1 cDNA increased E-cadherin expression and capacity for cellular aggregation, and suppressed cancer cell invasion. The expression of transcriptional suppressors of E-cadherin, Snail and ZEB1, were increased by CBR1 suppression, but suppressed by CBR1 overexpression. Immunohistochemical analyses showed that decreased CBR1 expression is significantly related with poor PFS and OS compared with strong CBR1 expression. In multivariate analyses, decreased CBR1 expression was an independent prognostic factor for PFS and OS. CBR1 regulates cancer cell invasion in endometrial adenocarcinomas by regulating the epithelial mesenchymal transition. A decreased CBR1 expression can be a useful marker of an unfavourable clinical outcome in patients with endometrial cancer. (C) 2012 Elsevier Ireland Ltd. All rights reserved.