EGF Protects Cells Against Dox-Induced Growth Arrest Through Activating Cyclin D1 Expression

被引:8
作者
Yao, Chun-Xia [1 ]
Shi, Jia-Chen [1 ]
Ma, Cai-Xia [1 ]
Xiong, Cheng-Juan [1 ]
Song, Yang-Liu [1 ]
Zhang, Shu-Feng [2 ]
Zhang, Shan-Feng [1 ]
Zang, Ming-Xi [1 ]
Xue, Li-Xiang [3 ]
机构
[1] Zhengzhou Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Zhengzhou 450001, Henan, Peoples R China
[2] Zhengzhou Univ, Peoples Hosp Henan Prov, Zhengzhou 450001, Henan, Peoples R China
[3] Peking Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
基金
中国国家自然科学基金;
关键词
CELL GROWTH; DOX; EGF; GATA-4; CYCLIN D1; GENE-EXPRESSION; CARDIOMYOCYTE PROLIFERATION; IN-VITRO; DIFFERENTIATION; DOXORUBICIN; GATA-4; CARCINOMA; APOPTOSIS; PATHWAY; VIVO;
D O I
10.1002/jcb.25134
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It has been reported that the antitumor drug doxorubicin (Dox) exerts its toxic effects via GATA-4 depletion and that over-expression of GATA-4 reverses Dox-induced toxicity and apoptosis; however, the precise mechanisms remain unclear. In this study, we observed, for the first time, that EGF protects cells against Dox-mediated growth arrest, G2/M-phase arrest, and apoptosis. Additionally, EGF expression was down-regulated in Dox-treated cells and up-regulated in GATA-4 over-expressing cells. Utilizing real-time PCR and western blotting analysis, we found that the expression of the cell cycle-associated protein cyclin D1 was inhibited in GATA-4-silenced cells and Dox-treated cells and was enhanced in GATA-4 over-expressing cells and EGF-treated cells. Furthermore, EGF treatment reversed the inhibited expression of cyclin D1 that was mediated by GATA-4 RNAi or Dox. Our results indicate that EGF, as a downstream target of Dox, may be involved in Dox-induced toxicity as well as in the protective role of GATA-4 against toxicity induced by Dox via regulating cyclin D1 expression, which elucidates a new molecular mechanism of Dox toxicity with important clinical implications. J. Cell. Biochem. 116: 1755-1765, 2015. (c) 2015 Wiley Periodicals, Inc.
引用
收藏
页码:1755 / 1765
页数:11
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