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.
Keywords: IRES; Ovarian cancer; Paclitaxel; β-Catenin.
Copyright © 2015 Elsevier Inc. All rights reserved.