Correlation of β-Catenin Localization with Cyclooxygenase-2 Expression and CpG Island Methylator Phenotype (CIMP) in Colorectal Cancer
| Autor: | Takako Kawasaki, Katsuhiko Nosho, Mutsuko Ohnishi, Yuko Suemoto, Gregory J. Kirkner, Reiko Dehari, Jeffrey A. Meyerhardt, Charles S. Fuchs, Shuji Ogino |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 9, Iss 7, Pp 569-577 (2007) |
| Druh dokumentu: | article |
| ISSN: | 1476-5586 1522-8002 |
| DOI: | 10.1593/neo.07334 |
| Popis: | The WNT/β-catenin (CTNNB1) pathway is commonly activated in the carcinogenic process. Cross-talks between the WNT and cyclooxygenase-2 (COX-2 or PTGS2)/prostaglandin pathways have been suggested. The relationship between (3-catenin activation and microsatellite instability (MSI) in colorectal cancer has been controversial. The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer, which is associated with MSI-high. However, no study has examined the relationship between (β-catenin activation and CIMP status. Using 832 population-based colorectal cancer specimens, we assessed (3-catenin localization by immunohistochemistry. We quantified DNA methylation in eight CIMP-specific promoters [CACNA1G, CDKN2A(p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1] by real-time polymerase chain reaction (MethyLight). MSI-high, CIMP-high, and BRAF mutation were associated inversely with cytoplasmic and nuclear (β-catenin expressions (i.e., β-catenin activation) and associated positively with membrane expression. The inverse relation between (β-catenin activation and CIMP was independent of MSI. COX-2 overexpression correlated with cytoplasmic (β-catenin expression (even after tumors were stratified by CIMP status), but did not correlate significantly with nuclear or membrane expression. In conclusion, β-catenin activation is inversely associated with CIMP-high independent of MSI status. Cytoplasmic β-catenin is associated with COX-2 overexpression, supporting the role of cytoplasmic β-catenin in stabilizing PTGS2(COX-2) mRNA. |
| Databáze: | Directory of Open Access Journals |
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