c-Jun blocks cell differentiation but not growth inhibition or apoptosis of chronic myelogenous leukemia cells induced by STI571 and by histone deacetylase inhibitors

Huei M. Huang, Juo Chuan Liu

研究成果: 雜誌貢獻文章

9 引文 斯高帕斯(Scopus)

摘要

The constitutively active Bcr-Abl tyrosine kinase plays a crucial role in chronic myelogenous leukemia (CML) pathogenesis. The Bcr-Abl protein induces the upregulation of proto-oncogene c-Jun, which is involved in Bcr-Abl transforming activity in Bcr-Abl positive cells. Recent studies reported that c-Jun inhibited hemoglobin synthesis in human CML cell line K562. However, c-Jun also plays a critical role in cell proliferation and apoptosis. In this study, we investigated the physiological roles of c-Jun in cell proliferation, apoptosis and erythroid differentiation of K562 cells. Firstly, we generated K562 cell lines stably overexpressing c-Jun. These clones have the same proliferation rate as the parental cell line in general culture medium. Endogenous c-Jun expression was analyzed to determine the effective concentration of STI571 for inhibiting Bcr-Abl signaling. Western blots show that STI571 inhibited c-Jun expression in a dose-dependent manner, reaching a maximum inhibition at 1 μM. STI571 could inhibit c-Jun expression in K562 cells, but not in c-Jun-overexpression cells. c-Jun did not alter growth inhibition and apoptotic induction by STI571 treatment, but inhibited STI571-induced erythroid differentiation. Moreover, c-Jun did not alter growth inhibition and apoptotic induction by histone deacetylase (HDAC) inhibitors (apicidin, sodium butyrate, and MS275) treatment, but inhibited HDAC inhibitors-induced erythroid differentiation. These results suggest that c-Jun may modulate anticancer drugs-induced cell differentiation but not growth inhibition and apoptosis in CML cells.

原文英語
頁(從 - 到)568-574
頁數7
期刊Journal of Cellular Physiology
218
發行號3
DOIs
出版狀態已發佈 - 三月 2009

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

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