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EGF Protects Cells Against Dox‐Induced Growth Arrest Through Activating Cyclin D1 Expression
Author(s) -
Yao ChunXia,
Shi JiaChen,
Ma CaiXia,
Xiong ChengJuan,
Song YangLiu,
Zhang ShuFeng,
Zhang ShanFeng,
Zang MingXi,
Xue LiXiang
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25134
Subject(s) - cyclin d1 , apoptosis , doxorubicin , microbiology and biotechnology , cell cycle , cyclin d , chemistry , programmed cell death , cyclin a , cyclin b , cell cycle checkpoint , cyclin b1 , biology , cancer research , cyclin dependent kinase 1 , biochemistry , chemotherapy , genetics
ABSTRACT 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. © 2015 Wiley Periodicals, Inc.