RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo

被引:84
作者
Cao, Xi-Xi [1 ]
Xu, Jing-Da [1 ]
Xu, Jia-Wen [1 ]
Liu, Xiao-Li [1 ]
Cheng, Yuan-Yuan [1 ]
Wang, Wen-Juan [1 ]
Li, Qing-Quan [1 ]
Chen, Qi [1 ]
Xu, Zu-De [1 ]
Liu, Xiu-Ping [1 ]
机构
[1] Fudan Univ, Dept Pathol, Shanghai Med Coll, Shanghai 200032, Peoples R China
关键词
RACK1; Breast carcinoma; Proliferation; Invasion/metastasis; Biomarker; PROTEIN-KINASE-C; PIK3CA GENE; P21-ACTIVATED KINASES; INTERACTING PROTEIN; HIGH-FREQUENCY; BINDS; INHIBITION; EXPRESSION; GROWTH; CANCER;
D O I
10.1007/s10549-009-0657-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
A yeast two-hybrid system was utilized to identify novel PI3K p110a-interacting proteins, of which receptor of activated protein kinase C1 (RACK1) was chosen for successive detailed analyses. Our aim was to investigate the function(s) of RACK1 and its involvement in mechanisms of breast carcinoma proliferation and invasion/metastasis. Experiments in breast carcinoma cell lines stably transfected with RACK1, as well as nude mouse models, showed that RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo. Conversely, knockdown of RACK1 by siRNA in vitro inhibited proliferation, migration, and invasion. In cell lines stably transfected with RACK1, p-AKT, cyclin D1, cyclin D3, and CD147 expression, as well as MMP2 activity, were elevated. RACK1-induced migration could be inhibited by the addition of Rho-kinase inhibitor. In 160 breast carcinoma cases, survival analyses established that RACK1 is an independent prognostic factor for poor outcome (P < 0.001). In conclusion, RACK1 is an independent prognosis-related factor and promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo.
引用
收藏
页码:375 / 386
页数:12
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