Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University, General Hospital, Tianjin, China.
J Mol Histol. 2011 Dec;42(6):491-8. doi: 10.1007/s10735-011-9347-1. Epub 2011 Sep 10.
Dickkopf-1 (DKK1) is an inhibitor of Wnt/β-catenin signaling pathway. High levels of DKK1 protein were found in a series of cancers. However, the role of DKK1 in the progression of esophageal carcinoma is not fully understood. In the present study, RT-PCR and Western blot were used to detect the expression of DKK1 in esophageal carcinoma tissues, matched adjacent normal esophageal tissues, and esophageal carcinoma cell lines. Our results showed that the expression of DKK1 was upregulated on both mRNA and protein levels in esophageal carcinoma tissues compared with the adjacent normal esophageal tissues, meanwhile, in four esophageal carcinoma cell lines analyzed, expression of DKK1 was detected with different levels. Immunohistochemistry and immunofluoresence revealed that the distribution of DKK1 was mainly in the cytoplasm in both carcinoma tissues and cell lines. To further explore the biological effects of DKK1 on proliferation, cell cycle and invasion capability, we constructed the eukaryotic expression vector pCMV-Tab-2b-DKK1 which can effectively overexpress DKK1. Subsequently, we observed that exogenous expression of DKK1 in EC9706 cell line resulted in an increased rate of proliferation, and S stage and G2/M stage ratio whereas G0/G1 ratio was decreased. In order to evaluate the invasion capability Boyden chamber was analyzed which implied that overexpression of DKK1 resulted in an increase in the invasion ability in EC9706 cell line. Taken together, the study indicates that DKK1 might be a key regulator in the progression of esophageal carcinoma and a potential therapeutic target in esophageal carcinoma.
Dickkopf-1 (DKK1) 是 Wnt/β-catenin 信号通路的抑制剂。在一系列癌症中发现 DKK1 蛋白水平升高。然而,DKK1 在食管癌进展中的作用尚不完全清楚。在本研究中,使用 RT-PCR 和 Western blot 检测了食管癌组织、配对的相邻正常食管组织和食管癌细胞系中 DKK1 的表达。我们的结果表明,与相邻的正常食管组织相比,食管癌组织中 DKK1 的表达在 mRNA 和蛋白水平上均上调,同时,在分析的四种食管癌细胞系中,检测到 DKK1 的表达水平不同。免疫组化和免疫荧光显示,在癌组织和细胞系中,DKK1 的分布主要在细胞质中。为了进一步探讨 DKK1 对增殖、细胞周期和侵袭能力的生物学影响,我们构建了能够有效过表达 DKK1 的真核表达载体 pCMV-Tab-2b-DKK1。随后,我们观察到在 EC9706 细胞系中外源表达 DKK1 导致增殖率增加,S 期和 G2/M 期比例增加,而 G0/G1 期比例降低。为了评估侵袭能力,我们进行了 Boyden 室分析,表明 DKK1 的过表达导致 EC9706 细胞系侵袭能力增加。综上所述,该研究表明 DKK1 可能是食管癌进展的关键调节因子,也是食管癌的潜在治疗靶点。