Different effects of MEK/ERK and PI3K/Akt signaling pathways in regulating TRAIL sensitivity of human leukemia cells

Fang Fang; Hong Suli; Feng Zhiyong; Yinqiang Xin; Wang Qi; Fu Jin; Xu Yimiao; Luo Lan; Zhimin Yin

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Different effects of MEK/ERK and PI3K/Akt signaling pathways in regulating TRAIL sensitivity of human leukemia cells

Fang Fang 1 * #,Hong Suli 1,Feng Zhiyong 1,Yinqiang Xin 1,Wang Qi 1,Fu Jin 1,Xu Yimiao 1,Luo Lan 2,Zhimin Yin 2

1.Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Science, Nanjing Normal University

2.Nanjing Normal University

*Correspondence author

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Subject:

Funding: grants from the National Nature Science Foundation of China;The Specialized Research Fund for the Doctoral Program of Higher Education（No.30770842;30771979;2007104SBJ0152）

Opened online:26 January 2010

Accepted by: none

Citation: Fang Fang,Hong Suli,Feng Zhiyong.Different effects of MEK/ERK and PI3K/Akt signaling pathways in regulating TRAIL sensitivity of human leukemia cells[OL]. [26 January 2010] http://en.paper.edu.cn/en_releasepaper/content/39417

In order to investigate the role of MEK/ERK and PI3K/Akt signaling pathways in regulating cell sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we have conducted a comparative study regarding the effects of TRAIL on these pathways. We showed that TRAIL-induced apoptosis may be differentially regulated by inhibitors of MEK/ERK (U0126) or PI3K/Akt (LY294002) pathway in TRAIL-sensitive (U937) and TRAIL-resistant (K562) human leukemia cells. U0126 increased, but LY294002 significantly decreased TRAIL-induced apoptosis in U937 cells. We also demonstrated that ERK1/2 phosphorylation upon TRAIL treatment was obviously increased in the presence of LY294002. Overexpression of HA-Akt-WT reduced ERK1/2 phosphorylation and increased cell apoptosis induced by TRAIL. Moreover, we found that MEK/ERK and PI3K/Akt pathways had opposite effects on Bad phosphorylation upon TRAIL treatment. In conclusion, our results suggest that the crosstalk between these two pathways and the activation of ERK1/2 play crucial roles in TRAIL- induced apoptosis.

Keywords:TRAIL;PI3K;ERK;Apoptosis

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