대장암에서 CDK8 및 β-catenin의 역할

Abstract

Colorectal adenocarcinoma is a major cause of morbidity and mortality in Korea. The Wnt/β-catenin pathway plays an important role in colon cancers. However, relatively little is known about the regulatory mechanism of β-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 β-catenin expressions, the author have conducted a population-based study for immunohistochemical staining analysis of tumor tissues, and Western blot analysis and CDK8 interference studies of colon cancer cell lines. Here, the author tested the hypothesis that colorectal cancers with CDK8 expression have distinct clinical, prognostic and molecular attributes. Among 127 colorectal cancers, CDK8 expression was detected in 96 (76%) tumors by immunohistochemistry. CDK8 and β-catenin expression had significant positive correlation with carcinogenesis, tumor progression and patients' survival. Immunohistochemically, CDK8 expression in colorectal cancer was independently associated with β-catenin activation (p=0.0002). However, β-catenin expression was not completely suppressed by CDK8 interference in colon cancer cell lines, HCT-116, HT-29 and SNU-C5. These data support a potential link between CDK8 and β-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 β-catenin regulation of general colon cancer.