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Gallbladder cancer is a malignancy with poor prognosis, predominantly resulting from invasion and metastasis. Our previous studies have demonstrated that prostaglandin E2 (PGE2), generated by cyclooxygenase 2 (Cox-2), transactivates epidermal growth factor receptor (EGFR), c-Met and β-catenin; thus, enhancing colon cancer cell growth and invasiveness
Thirty-five specimens of invasive gallbladder cancer, 8
Cox-2, c-Met, β-catenin, c-erbB2 and EGFR were over-expressed in 80, 74, 71, 62 and 11% of invasive gallbladder cancers, respectively. β-catenin was expressed in 80% of non-malignant specimens, exclusively in the cell membrane, while the cancer specimens showed cytoplasmic and/or nuclear staining. Significantly higher Cox-2, c-Met and β-catenin expressions were present in cancer cells of the invasive front than in the tumor central areas (p<0.001), and these expressions were significantly (p=0.01) associated with the invasion depth. Co-expressions of Cox-2, c-Met, β-catenin and c-erbB2 were present in 42% of the specimens in cancer cells forming the invasive front.
The overexpressions, and often co-localizations, of Cox-2, c-Met and β-catenin in cancer cells forming the invasive front indicate their local interactions and important roles in invasion.
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