The nucleocytoplasmic translocation and up-regulation of ING5 protein in breast cancer: a potential target for gene therapy
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Xiao-Qing Ding1, Shuang Zhao1, Lei Yang1, Xin Zhao1, Gui-Feng Zhao1, Shu-Peng Zhao2, Zhi-Jie Li1 and Hua-Chuan Zheng1
1Department of Experimental Oncology and Animal Center, Shengjing Hospital of China Medical University, Shenyang 110004, China
2Department of Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China
Hua-Chuan Zheng, email: [email protected]
Keywords: breast cancer, ING5, pathogenesis, aggressiveness, progression
Received: January 16, 2017 Accepted: May 03, 2017 Published: May 17, 2017
Here, we found that ING5 overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial–transition of breast cancer cells. It also suppressed the tumor growth of breast cancer cells by inhibiting proliferation, inducing apoptosis and autophagy. ING5-mediated chemoresistance was positively linked to Akt and NF-κB activation, MRP1 and GST-π overexpression, and FBXW7 hypoexpression. ING5 expression was higher in breast cancer than normal tissue at both mRNA and protein levels. ING5 mRNA expression was positively correlated with relapse- and distant metastasis-free survival rates. Nuclear ING5 expression showed gradual decrease from breast normal tissue, fibroadenoma, adenomatosis, primary to metastatic cancers, while versa for cytoplasmic ING5. Nuclear ING5 expression was negatively correlated with distant metastasis and p53 hypoexpression, while cytoplasmic ING5 expression was positively correlated with tumor size and ER expression. These data suggested that up-regulated expression and nucleocytoplasmic translocation of ING5 protein were observed in breast cancer. The higher expression of nuclear ING5 was inversely linked to worse clinicopathological behaviors of breast cancer by in vivo and vitro reversing aggressive phenotypes. Therefore, it should be employed as a biomarker to indicate the tumorigenesis and aggressiveness of breast cancer, and as a potential target for gene therapy.
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