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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/4582


    Title: Myeloid cell leukemia-1 inversely correlates with glycogen synthase kinase-3beta activity and associates with poor prognosis in human breast cancer
    Authors: Qingqing Ding;Weiya Xia;Jung-Mao Hsu;Chun-Te Chen;Long-Yuan Li;Dung-Fang Lee;Jer-Yen Yang;Xiaoming Xie;Jaw-Ching Liu;Mien-Chie Hung
    Date: 2007-05
    Issue Date: 2009-11-27 13:56:55 (UTC+8)
    Publisher: Asia University
    Abstract: Myeloid cell leukemia-1 (Mcl-1), an antiapoptotic Bcl-2 family member, is overexpressed in many types of human cancer and associates with cell immortalization, malignant transformation, and chemoresistance. Glycogen synthase kinase-3beta (GSK-3beta), a key component of the Wnt signaling pathway, is involved in multiple physiologic processes such as protein synthesis, tumorigenesis, and apoptosis. Here, we report that expression of Mcl-1 was correlated with phosphorylated GSK-3beta (p-GSK-3beta) at Ser(9) (an inactivated form of GSK-3beta) in multiple cancer cell lines and primary human cancer samples. In addition, Mcl-1 was strikingly linked with poor prognosis of human breast cancer, in which the high level of Mcl-1 was related to high tumor grade and poor survival of breast cancer patients. Furthermore, we found that activation of GSK-3beta could down-regulate Mcl-1 and was required for proteasome-mediated Mcl-1 degradation. Under some physiologic conditions, such as UV irradiation, anticancer drug treatment, and inhibition of growth factor pathways, Mcl-1 was down-regulated through activation of GSK-3beta. Our results indicate that Mcl-1 stabilization by GSK-3beta inactivation could be involved in tumorigenesis and serve as a useful prognostic marker for human breast cancer.
    Relation: CANCER RESEARCH 10(67):4564-4571
    Appears in Collections:[生物科技學系] 期刊論文

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