Roles of cyclin-dependent kinase 8 and β-catenin in the oncogenesis and progression of gastric adenocarcinoma.

Gastric adenocarcinoma is a common cause of cancer-related death. 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, we conducted a study of immuno-histochemical staining of tumor tissues (12 adenomas, 24 early gastric carcinomas, 24 advanced gastric carcinomas and 21 metastatic lymph nodes), together with Western blot analysis and CDK8 interference studies using gastric cancer cell lines. Gastric adenocarcinomas with CDK8 expression had distinct clinical, prognostic and molecular attributes. CDK8 expression and the delocalization of β-catenin expression showed a significant positive correlation with carcinogenesis and tumor progression, especially lymph node metastasis. Immunohisto-chemically, CDK8 expression in gastric adenocarcinoma was independently associated with β-catenin activation (p<0.05). β-catenin expression was suppressed by CDK8 interference in the gastric adenocarcinoma cell lines, SNU-601 and SNU-638. These data support the potential link between CDK8 and β-catenin, and suggest that CDK8 detection and β-catenin delocalization could be related to a poor prognosis. Moreover, the interference of CDK8 could be a promising therapeutic modality for gastric adenocarcinoma.