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视黄酸 X 受体α和β-连环蛋白表达的抑制与结直肠癌的进展显著相关。

Suppression of retinoid X receptor alpha and aberrant β-catenin expression significantly associates with progression of colorectal carcinoma.

机构信息

Department of Pathology, The First Affiliated Hospital and Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.

出版信息

Eur J Cancer. 2011 Sep;47(13):2060-7. doi: 10.1016/j.ejca.2011.04.010. Epub 2011 May 9.

Abstract

To investigate retinoid X receptor alpha (RXRα) and β-catenin expression and their relationship with the clinicopathological features of colorectal carcinoma (CRC). Real-time PCR and western blot analyses revealed that β-catenin and RXRα expression at both mRNA and protein levels in four pairs of fresh CRC and adjacent non-tumour tissues (ANT) dramatically was increased and decreased in CRC compared with ANT, respectively. Furthermore, RXRα expression at both mRNA and protein levels was downregulated in higher histological grade CRC. Immunohistochemistry staining in 120 cases of CRC and 60 cases of lymph node metastatic carcinoma of CRC showed that RXRα expression was significantly suppressed in CRC compared with ANT (P<0.001) and low expression of RXRα in CRC was significantly associated with histological grade (P<0.001), TNM stage (P=0.022) and N classification (P=0.002). The aberrant (accumulated cytoplasm or/and nuclei) expression of β-catenin was higher in CRC than that in ANT (P<0.001) and associated with histological grade (P=0.001) and N classification (P=0.002). Moreover, there was a close relationship between low RXRα expression and aberrant β-catenin expression in CRC (P=0.032). Taken together with our previous study, aberrant β-catenin expression upregulated by suppression of RXRα may play a crucial role in pathogenesis and progression of CRC.

摘要

目的

研究维甲酸 X 受体α(RXRα)和β-连环蛋白的表达及其与结直肠癌(CRC)临床病理特征的关系。

方法

采用实时 PCR 和 Western blot 分析技术检测 4 对新鲜结直肠癌及相应癌旁组织中β-连环蛋白和 RXRα的 mRNA 和蛋白表达。

结果

与癌旁组织相比,CRC 中β-连环蛋白和 RXRα的 mRNA 和蛋白表达水平均显著升高和降低。此外,RXRα在高组织学分级 CRC 中的表达水平下调。免疫组化染色显示,与癌旁组织相比,CRC 中 RXRα的表达显著降低(P<0.001),且 RXRα低表达与组织学分级(P<0.001)、TNM 分期(P=0.022)和 N 分类(P=0.002)显著相关。CRC 中β-连环蛋白的异常(细胞质和/或细胞核累积)表达高于癌旁组织(P<0.001),且与组织学分级(P=0.001)和 N 分类(P=0.002)显著相关。此外,CRC 中 RXRα低表达与β-连环蛋白异常表达密切相关(P=0.032)。

结论

RXRα表达下调导致β-连环蛋白异常表达可能在 CRC 的发病机制和进展中起关键作用。

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