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The activation of ERK1/2 via a tyrosine kinase pathway attenuates trail-induced apoptosis in HeLa cells

Cited 18 time in Web of Science Cited 17 time in Scopus
Authors
Lee, Myoung Woo; Bach, Jae Hyun; Lee, Hyun Jung; Lee, Do Yeon; Joo, Wan Seok; Kim, Yong Sik; Park, Soon Cheol; Kim, Kyung Yong; Lee, Won Bok; Kim, Sung Su
Issue Date
2005-11-25
Publisher
Taylor & Francis
Citation
Cancer Invest. 2005;23(7):586-92.
Keywords
*ApoptosisApoptosis Regulatory Proteins/*physiologyDown-RegulationEnzyme ActivationGenes, bcl-2Hela CellsHumansMembrane Glycoproteins/*physiologyMitogen-Activated Protein Kinase 3/*metabolismProtein-Tyrosine Kinases/metabolismSignal TransductionTNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor-alpha/*physiologyUp-Regulation
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves as an extracellular signal that triggers apoptosis in tumor cells. To characterize the molecular events involved in TRAIL-induced apoptotic signaling, we investigated the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in HeLa cell death. Here we show that TRAIL-activated ERK1/2 through a tyrosine kinase-dependent pathway, subsequently elevated anti-apoptotic Bcl-2 protein levels. ERK1/2 inhibition with PD98059 promoted apoptotic cell death through the downregulation of ERK1/2 activity and Bcl-2 protein levels. Moreover, tyrosine kinase inhibition with Genistein in TRAIL-induced apoptosis effectively attenuated ERK1/2 activity and enhanced apoptotic cell death. Taken together, our results indicate that ERK1/2 activation via tyrosine kinase pathway plays a protective role as the cellular defense mechanism through the upregulation of Bcl-2 protein levels in TRAIL-induced apoptosis.
ISSN
0735-7907 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16305985

http://hdl.handle.net/10371/26605
DOI
https://doi.org/10.1080/07357900500283036
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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