The mechanism of overactivation of the Wnt signaling in leukemic cells

• Main Authors: Jen-Chin Tong, 湯仁智
• Other Authors: Chien-Hui Lieu
• Format: Others
• Language: en_US
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/32640724773793590317

碩士 === 國立陽明大學 === 醫學生物技術研究所 === 95 === The Wnt/beta-catenin signaling pathway can promote stem cell self-renewal and is dysregulated in colon carcinoma. Wnt activation leads to beta-catenin accumulation, nuclear translocation and interaction with T-cell factor/ lymphoid enhancer factor (TCF/LEF) transcription factors to regulate genes important for stem cells development and proliferation.�nbeta-catenin is a core of the canonical Wnt signaling pathway. Activation of the Wnt/beta-catenin pathway has recently been shown to be crucial to the development of leukemic stem cells in chronic myeloid leukemia and acute myeloid leukemia. In this study, we examined the mechanism of beta-catenin accumulation in three leukemia cell lines. Wnt antagonist protein Dkk-1 treatment can not reverse beta-catenin accumulation in Jurkat and U937 cells. This suggests that the beta-catenin accumulation does not result from stimulation from extrinsic Wnt protein. On the other hand, the mRNA of ��-catenin and Axin in Jurkat cells was more labile than normal PBMNC. Quantification real-time RT-PCR experiment revealed mRNA expression ratio of beta-catenin/APC/Axin/GSK-3beta was imbalanced. Examining the stability of beta-catenin degradation complex and the immunoprecipitation studies suggest that this complex is intact and function well in Jurkat leukemic cell. The overactivation of Wnt signaling might result from imbalance of the complex members, especially the APC and Axin. In addition, the beta-TrCP expression was activated in response to beta-catenin. Therefore, beta-TrCP can be a potent indicator for activation of Wnt signaling in leukemic cells.