Cross-talk between PI3K/Akt and MEK/ERK pathways regulates human hepatocellular carcinoma cell cycle progression under endoplasmic reticulum stress.
- VernacularTitle:Akt和胞外信号调节激酶通路间的信号交流对内质网应激条件下肝癌细胞周期的调控
- Author:
Dong-mei YAN
1
;
Rong-yang DAI
;
Chun-yan DUAN
;
Shao-kun CHEN
;
You-ping LIU
;
Chuan-ning CHEN
;
Hong LI
Author Information
- Publication Type:Journal Article
- MeSH: Butadienes; pharmacology; Carcinoma, Hepatocellular; metabolism; Cell Cycle; Cell Line, Tumor; Chromones; pharmacology; Endoplasmic Reticulum; metabolism; Extracellular Signal-Regulated MAP Kinases; metabolism; Humans; Mitogen-Activated Protein Kinase Kinases; antagonists & inhibitors; metabolism; Morpholines; pharmacology; Nitriles; pharmacology; Phosphatidylinositol 3-Kinase; metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt; antagonists & inhibitors; metabolism; Signal Transduction
- From: Chinese Journal of Hepatology 2010;18(12):909-914
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the cross-talk between the PI3K/Akt and MEK/ERK pathways and its role in cell cycle regulation under endoplasmic reticulum stress in human hepatocellular carcinoma cells.
METHODSPI3K inhibitor LY294002 and MEK inhibitor U0126 were used to block the PI3K/Akt and MEK/ERK pathways respectively, and constitutively activated Akt mutant construct was used to activate the PI3K/Akt pathway. Western blot was used to study the potential cross-talk between the PI3K/Akt and MEK/ERK pathways under endoplasmic reticulum stress in human hepatocellular carcinoma cells. the role of the cross-talk between the PI3K/Akt and MEK/ERK pathways in cell cycle regulation was investigated by using propidium iodide staining.
RESULTSLY294002 not only blocked Akt activation efficiently but also increased ERK phosphorylation markedly under endoplasmic reticulum stress in SMMC-7721 and Hep3B cells. Furthermore, myr-Akt inhibited endoplasmic reticulum stress-mediated ERK phosphorylation. In contrast, MEK inhibitor U0126 had no effect on endoplasmic reticulum stress-induced Akt activation. It is notable that both myr-Akt overexpression and MEK inhibitor U0126 inhibited endoplasmic reticulum stress-induced G0/G1 phase arrest in SMMC-7721 cells.
CONCLUSIONEndoplasmic reticulum stress-induced Akt activation is mediated through PI3K and the PI3K/Akt pathway inactivation is involved in increased ERK activity in human hepatocellular carcinoma cells. The cross-talk between the PI3K/Akt and MEK/ERK cascades plays an important role in endoplasmic reticulum stress-induced human hepatocellular carcinoma cell cycle arrest.
