TY - JOUR
T1 - Myeloid cell leukemia-1 inversely correlates with glycogen synthase kinase-3β activity and associates with poor prognosis in human breast cancer
AU - Ding, Qingqing
AU - He, Xianghuo
AU - Xia, Weiya
AU - Hsu, Jung Mao
AU - Chen, Chun-Te
AU - Li, Long Yuan
AU - Lee, Dung Fang
AU - Yang, Jer Yen
AU - Xie, Xiaoming
AU - Liu, Jaw Ching
AU - Hung, Mien Chie
PY - 2007/5/15
Y1 - 2007/5/15
N2 - 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-3β (GSK-3β), 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-3β (p-GSK-3β) at Ser 9 (an inactivated form of GSK-3β) 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-3β 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-3β. Our results indicate that Mcl-1 stabilization by GSK-3β inactivation could be involved in tumorigenesis and serve as a useful prognostic marker for human breast cancer.
AB - 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-3β (GSK-3β), 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-3β (p-GSK-3β) at Ser 9 (an inactivated form of GSK-3β) 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-3β 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-3β. Our results indicate that Mcl-1 stabilization by GSK-3β inactivation could be involved in tumorigenesis and serve as a useful prognostic marker for human breast cancer.
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U2 - 10.1158/0008-5472.CAN-06-1788
DO - 10.1158/0008-5472.CAN-06-1788
M3 - Article
C2 - 17495324
AN - SCOPUS:34250327394
SN - 0008-5472
VL - 67
SP - 4564
EP - 4571
JO - Cancer Research
JF - Cancer Research
IS - 10
ER -