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Specific Inhibition of β-Catenin in Jeko-1 Mantle Cell Lymphoma Cell Line Decreases Proliferation and Induces Apoptosis

BACKGROUND: The canonical Wnt signaling pathway has been considered as a potent oncogenic signaling in the initiation and progression of hematological malignancies. As a key regulator of the Wnt signaling pathway, the role of β-catenin in mantle cell lymphoma (MCL) pathogenesis and progression was i...

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Detalles Bibliográficos
Autores principales: He, Jinshui, Huang, Yiqun, Weng, Jianmin, Xiao, Liyun, Weng, Kaizhi, Ma, Xudong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554364/
https://www.ncbi.nlm.nih.gov/pubmed/26227550
http://dx.doi.org/10.12659/MSM.893514
Descripción
Sumario:BACKGROUND: The canonical Wnt signaling pathway has been considered as a potent oncogenic signaling in the initiation and progression of hematological malignancies. As a key regulator of the Wnt signaling pathway, the role of β-catenin in mantle cell lymphoma (MCL) pathogenesis and progression was investigated in this study. MATERIAL/METHODS: A total of 30 MCL samples were collected from patients and were examined for the expression of β-catenin and p-GSK3β using immunohistochemical (IHC) staining. Further in vitro studies employed MTT and Western blot assays detecting proliferation and apoptosis-related proteins in MCL cell line Jeko-1, which were transfected with β-catenin shRNA or specific inhibitor XAV939. RESULTS: Expression of β-catenin and phosphorylated glycogen synthase kinase-3 beta (p-GSK3β) in MCL was significantly higher than those in controlled samples. In vitro studies indicated that β-catenin knockdown significantly inhibited cell proliferation and induced apoptosis in Jeko-1 cells. Furthermore, XAV939 induced apoptosis and growth arrest in Jeko-1 cells. Both inhibitory agents increased Bax and caspase 3 proteins, and decreased Bcl-2, c-Myc, and Cyclin D1 proteins. CONCLUSIONS: The specific inhibition of β-catenin induces apoptosis and growth arrest, making it a potential therapeutic target against MCL.