Department of Pathology, Chosun University School of Medicine, Gwangju, Republic of Korea.
Oncol Rep. 2010 Jul;24(1):285-91.
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.
结直肠腺癌是发病率和死亡率的主要原因。Wnt/β-连环蛋白途径在结肠癌中起着重要作用。然而，关于β-连环蛋白在结肠癌中的调节机制知之甚少。CDK8 是中介复合物的细胞周期蛋白依赖性激酶 (CDK) 成员，将转录调节剂与基本转录机制偶联，并且涉及与结肠癌相关的关键途径的转录调节。为了确定 CDK8 和β-连环蛋白表达之间的关系，进行了一项基于人群的研究，对肿瘤组织进行了免疫组织化学染色分析，并对结肠癌细胞系进行了 Western blot 分析和 CDK8 干扰研究。测试了具有 CDK8 表达的结直肠癌具有独特的临床、预后和分子特征的假设。在 127 例结直肠癌中，96 例（76%）肿瘤通过免疫组织化学检测到 CDK8 表达。CDK8 和β-连环蛋白表达与癌变、肿瘤进展和患者生存有显著的正相关。免疫组织化学分析显示，结直肠癌中 CDK8 的表达与β-连环蛋白的激活独立相关（P=0.0002）。然而，在结肠癌细胞系 HCT-116、HT-29 和 SNU-C5 中，CDK8 干扰并不能完全抑制β-连环蛋白的表达。这些数据支持 CDK8 和β-连环蛋白之间存在潜在联系，并表明 CDK8 可能鉴定出一组预后不良的结肠癌患者。然而，通过β-连环蛋白调节一般结肠癌，控制 CDK8 不是一种有效的治疗策略。
