The role of tyrosine kinase etk/bmx in egf-induced apoptosis of mda-mb-468 breast cancer cells

ABSTRACT 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 adenovirus 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. Access through your institution Buy or

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IL-26 MEDIATES EPIDERMAL GROWTH FACTOR RECEPTOR-TYROSINE KINASE INHIBITOR RESISTANCE THROUGH ENDOPLASMIC RETICULUM STRESS SIGNALING PATHWAY IN TRIPLE-NEGATIVE BREAST CANCER CELLS Article

Open access 21 May 2021 ERBB2/HER2-DEPENDENT DOWNREGULATION OF A CELL DEATH-PROMOTING PROTEIN BLNK IN BREAST CANCER CELLS IS REQUIRED FOR 3D BREAST TUMOR GROWTH Article Open access 06 August

2022 MAP KINASE ERK5 MODULATES CANCER CELL SENSITIVITY TO EXTRINSIC APOPTOSIS INDUCED BY DEATH-RECEPTOR AGONISTS Article Open access 02 November 2023 ABBREVIATIONS * Etk: epithelial and

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ACKNOWLEDGEMENTS This work was supported by the intramural funds of the National Health Research Institutes (to H-MS), and in part by the National Institute of Health Research Grants CA39207

and 91574 (to HJK) and R01 DE 10742 and DE14183 (to DKA). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, ROC,

Taiwan Kai-Yun Chen & Hsiu-Ming Shih * Division of Molecular and Genomic Medicine, National Health Research Institutes, Taipei, ROC, Taiwan Kai-Yun Chen, Li-Ming Huang & Hsiu-Ming

Shih * University of California at Davis Cancer Center, Sacramento, California, 95817, CA, USA Hsing-Jien Kung * Department of Molecular Pharmacology and Toxicology, University of Southern

California, Los Angeles, 90033, CA, USA David K Ann Authors * Kai-Yun Chen View author publications You can also search for this author inPubMed Google Scholar * Li-Ming Huang View author

publications You can also search for this author inPubMed Google Scholar * Hsing-Jien Kung View author publications You can also search for this author inPubMed Google Scholar * David K Ann

View author publications You can also search for this author inPubMed Google Scholar * Hsiu-Ming Shih View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHOR Correspondence to Hsiu-Ming Shih. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc). SUPPLEMENTARY

INFORMATION SUPPLEMENTARY DATA (JPG 59 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Chen, KY., Huang, LM., Kung, HJ. _et al._ The role of tyrosine

kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells. _Oncogene_ 23, 1854–1862 (2004). https://doi.org/10.1038/sj.onc.1207308 Download citation * Received: 16 August

2003 * Revised: 22 October 2003 * Accepted: 22 October 2003 * Published: 15 December 2003 * Issue Date: 11 March 2004 * DOI: https://doi.org/10.1038/sj.onc.1207308 SHARE THIS ARTICLE Anyone

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Springer Nature SharedIt content-sharing initiative KEYWORDS * Etk kinase * EGF-induced * apoptosis * Statl activation