Role of CDK8 and beta-catenin in colorectal adenocarcinoma.
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.
Seo
Jong-Og
JO
Department of Pathology, Chosun University School of Medicine, Gwangju, Republic of Korea.
Han
Song Iy
SI
Lim
Sung-Chul
SC
D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D056850:Cyclin-Dependent Kinase 8 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000378:metabolism / Q000502:physiology*
D034741:RNA, Small Interfering; D051176:beta Catenin; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8