위샘암종의 발생 및 진행에서 cyclin-dependent kinase 8과 β-catenin의 역할

Abstract

Gastric adenocarcinoma is the second most common cause of cancer-related death in the world. The Wnt/β-catenin pathway plays an important role in various cancers. However, relatively little is known about the regulatory mechanism of β-catenin in stomach cancer. To determine the patterns of cyclin-dependent kinase (CDK) 8 and β-catenin expression and the relationship between CDK8 and β-catenin, the author has conducted a study for immunohistochemical staining analysis of tumor tissues (12 adenomas, 24 early gastric carcinomas, 24 advanced gastric carcinomas, and 21 metastatic lymph nodes), and Western blot analysis and CDK8 interference studies of gastric cancer cell lines. Gastric adenocarcinomas with CDK8 expression had distinct clinical, prognostic and molecular attributes. CDK8 stainability and delocalization of β-catenin expression showed a significant positive correlation with carcinogenesis and tumor progression, especially lymph node metastasis. Immunohistochemically, CDK8 expression in gastric adenocarcinoma was independently associated with β-catenin activation (p<0.05). β-catenin expression was suppressed by CDK8 interference in gastric adenocarcinoma cell lines SNU-601 and SNU-638 cells. These data support a potential link between CDK8 and β-catenin, and suggest that CDK8 stainability and β-catenin delocalization may be related to a poor prognosis. Moreover, the interference of CDK8 could be a promising therapeutic modality of gastric adenocarcinoma.