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Biochemical and biophysical research communications

β-Catenin expression is regulated by an IRES-dependent mechanism and stimulated by paclitaxel in human ovarian cancer cells.


PMID 25849888

Abstract

Paclitaxel (PTX) is commonly used in the chemotherapy of ovarian cancer, but resistance occurs in most cases, allowing cancer progression. The Wnt/β-catenin pathway has been associated with this resistance, but there are no reports on the regulation of β-catenin expression at the translational level. In the present study, we found that PTX induced different transcription and translation levels of β-catenin in the human ovarian cancer cell lines A2780 and SKOV3. We also demonstrated that β-catenin mRNA contained an internal ribosome entry segment (IRES) that regulated its translation. Using gene transfection and reporter assays, we revealed that the entire CTNNB1 5'-untranslated region (UTR) contributed to IRES activity. Interestingly, we found that c-myc and cyclin D1 increased significantly in transfected cells with increasing PTX concentration, and cell-survival rates remained at 60% while the PTX concentration increased. Suppressing β-catenin resulted in decreased expression of c-myc and cyclin D1 and made these cells less resistant. These results indicate that β-catenin translation is initiated via the IRES and this is regulated by PTX, suggesting that regulation of the IRES-dependent translation of β-catenin may be involved in the cancer cell response to PTX treatment.