The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

Kai Yun Chen, Li Ming Huang, Hsing Jien Kung, David K. Ann, Hsiu Ming Shih

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34 引文 斯高帕斯(Scopus)

摘要

Etk/Bmx, a member of the Tec family of tyrosine kinases, mediates various signaling pathways and confers several cellular functions. In the present study, we have explored the functional role of Etk in mediating EGF-induced apoptosis, using MDA-MB-468 cell line as a model. We first demonstrated that EGF treatment induces Etk tyrosine phosphorylation in both HeLa and MDA-MB-468 cells. Overexpression of Etk by recombinant adeno-virus in MDA-MB-468 cells potentiates the extent of EGF-induced cell apoptosis. The observed Etk-enhanced MDA-MB-468 cell apoptosis is associated with the Stat1 activation, as demonstrated by electrophoresis mobility shift assays and reporter gene assays. By contrast, a kinase domain deletion mutant EtkΔK, functioning as a dominant-negative mutant, ameliorates EGF-induced Stat1 activation and apoptosis in MDA-MB-468 cells. To explore whether the activated Etk alone is sufficient for inducing apoptosis, a conditionally activated Etk (ΔEtk-ER), a chimeric fusion protein of PH domain-truncated Etk and ligand-binding domain of estrogen receptor, was introduced into MDA-MB-468 cells. Upon β-estradiol ligand activation, the ΔEtk-ER could stimulate Stat1 activity and confer cell apoptosis independent of EGF treatment. Taken together, our findings indicate that Etk is a downstream signaling molecule of EGF receptor and suggest that Etk activation is essential for transducing the EGF-induced apoptotic signaling.
原文英語
頁(從 - 到)1854-1862
頁數9
期刊Oncogene
23
發行號10
DOIs
出版狀態已發佈 - 3月 11 2004
對外發佈

ASJC Scopus subject areas

  • 分子生物學
  • 癌症研究
  • 遺傳學

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