Role of CDK8 and β-catenin in colorectal adenocarcinoma
Role of CDK8 and β-catenin in colorectal adenocarcinoma
复制标题
DOI：
10.3892/or_00000858
复制
发表时间：
2010-07-01
期刊：
影响因子：
4.2
通讯作者：
Lim, Sung-Chul
中科院分区：
文献类型：
--
作者：
Seo, Jong-Og;Han, Song Iy;Lim, Sung-Chul
结直肠腺癌是发病率和死亡率的主要原因。Wnt/β-连环蛋白通路在结肠癌中起着重要作用。然而，对β-连环蛋白在结肠癌中的调控机制知之甚少。CDK 8是介体复合物的细胞周期蛋白依赖性激酶（CDK）成员，其将转录调节因子偶联至基础转录机制，并且涉及结肠癌中涉及的关键途径的转录调节。为了确定CDK 8和β-连环蛋白表达之间的关系，进行了基于人群的研究，用于肿瘤组织的免疫组织化学染色分析，以及结肠癌细胞系的Western印迹分析和CDK 8干扰研究。检验了CDK 8表达的结直肠癌具有不同的临床、预后和分子属性的假设。在127例结直肠癌中，96例（76%）通过免疫组化检测到CDK 8表达。CDK 8和beta-catenin表达与胃癌的发生、发展及患者生存期呈正相关。免疫组化显示，结直肠癌中CDK 8表达与β-连环蛋白激活独立相关（P=0.0002）。然而，在结肠癌细胞系HCT-116、HT-29和SNU-C5中，β-连环蛋白表达没有被CDK 8干扰完全抑制。这些数据支持CDK 8和β-连环蛋白之间的潜在联系，并表明CDK 8可以识别预后不良的结肠癌患者的子集。然而，通过β-连环蛋白调节一般结肠癌来控制CDK 8并不是有效的治疗策略。
Colorectal adenocarcinoma is a major cause of morbidity and mortality. The Wnt/beta-catenin pathway plays an important role in colon cancers. However, relatively little is known about the regulatory mechanism of beta-catenin in colon cancers. CDK8 is a cyclin-dependent kinase (CDK) member of the mediator complex that couples transcriptional regulators to the basal transcriptional machinery, and is implicated in the transcriptional regulation of key pathways involved in colon cancers. To determine the relationship between CDK8 and beta-catenin expressions, a population-based study was conducted for immunohistochemical staining analysis of tumor tissues, and Western blot analysis and CDK8 interference studies of colon cancer cell lines. The hypothesis that colorectal cancers with CDK8 expression have distinct clinical, prognostic and molecular attributes was tested. Among 127 colorectal cancers, CDK8 expression was detected in 96 (76%) tumors by immunohistochemistry. CDK8 and beta-catenin expression had significant positive correlation with carcinogenesis, tumor progression and patient survival. Immunohistochemically, CDK8 expression in colorectal cancer was independently associated with beta-catenin activation (P=0.0002). However, beta-catenin expression was not completely suppressed by CDK8 interference in the colon cancer cell lines HCT-116, HT-29 and SNU-C5. These data support a potential link between CDK8 and beta-catenin, and suggest that CDK8 may identify a subset of colon cancer patients with a poor prognosis. However, control of CDK8 is not an effective therapeutic strategy through beta-catenin regulation of general colon cancer.