title: β-Catenin expression is regulated by an IRES-dependent mechanism and stimulated by paclitaxel in human ovarian cancer cells.
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.
authors: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors: Qianyun
authors: Q
authors: Fu
authors: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors: Zhen
authors: Z
authors: Chen
authors: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors: Xiaohai
authors: X
authors: Gong
authors: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors: Yanfei
authors: Y
authors: Cai
authors: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors: Yun
authors: Y
authors: Chen
authors: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors: Xin
authors: X
authors: Ma
authors: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China. Electronic address: ry_zhu@sina.com.
authors: Ruiyu
authors: R
authors: Zhu
authors: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China. Electronic address: jinjian31@126.com.
authors: Jian
authors: J
authors: Jin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage*; D012270:Ribosomes / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051176:beta Catenin; D017239:Paclitaxel
keywords: IRES; Ovarian cancer; Paclitaxel; β-Catenin