PMID- 19998339
OWN - NLM
STAT- MEDLINE
DCOM- 20100720
LR  - 20161125
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 127
IP  - 4
DP  - 2010 Aug 15
TI  - ERK/MAPK activation involves hypoxia-induced MGr1-Ag/37LRP expression and 
      contributes to apoptosis resistance in gastric cancer.
PG  - 820-9
LID - 10.1002/ijc.25098 [doi]
AB  - We previously demonstrated that hypoxia increased the hypoxia-inducible factor 
      (HIF-1)-dependent MGr1-Ag/37LRP expression, which enhanced adhesion of gastric 
      cancer cells to laminin, inhibited drug-induced apoptosis and caused cell 
      adhesion-mediated drug resistance (CAM-DR). Here, we investigated the role of 
      extracellular-regulated kinase (ERK) 1/2 in the signaling mechanisms underlying 
      these events. We found that hypoxia activated ERK activity in vitro and in vivo. 
      Overexpression of mitogen-activated protein kinase (MAPK) kinase (MEK), which 
      preferentially activated ERK, mimics, in a nonadditive way, hypoxia-induced 
      activity of MGr1-Ag/37LRP promoter and expression of MGr1-Ag/37LRP. Furthermore, 
      U0126, the MEK inhibitor, inhibited hypoxia- and MEK-induced MGr1-Ag/37LRP 
      promoter activity in a dose-dependent manner. MEK inhibition also reversed 
      hypoxia- and MEK-induced HIF-1 protein and its activity in a dose-dependent 
      manner. We also investigated reactive oxygen species signaling this response. 
      Exogenous addition of H(2)O(2) was sufficient to activate ERK in a dose-dependent 
      profile. Reactive oxygen species scavengers of H(2)O(2) significantly inhibited 
      hypoxia-induced ERK or HIF-1 activation and sequential expression of 
      MGr1-Ag/37LRP. We also investigated the signaling in hypoxia-induced cell 
      adhesion and apoptosis induced by vincristine. Hypoxia significantly enhanced 
      adhesion of SGC7901 cells to laminin in a time-dependent manner, which might be 
      inhibited by the MEK inhibitor U0126 and MGr1-Ag/37LRP siRNA. Consistent with 
      results of adhesion assay, hypoxia-resistant apoptosis might be reversed by U0126 
      in a dose-dependent manner. Our results suggest that hypoxia-elicited 
      MGr1-Ag/37LRP expression activated by HIF-1 depends on ERK activation. These 
      events are dependent of reactive oxygen intermediates.
FAU - Liu, Lili
AU  - Liu L
AD  - Department of Pathology and Pathophysiology, Fourth Military Medical University, 
      Xi'an, China.
FAU - Zhang, Hongbo
AU  - Zhang H
FAU - Sun, Li
AU  - Sun L
FAU - Gao, Yuqi
AU  - Gao Y
FAU - Jin, Haifeng
AU  - Jin H
FAU - Liang, Shuhui
AU  - Liang S
FAU - Wang, Yanxia
AU  - Wang Y
FAU - Dong, Mingqing
AU  - Dong M
FAU - Shi, Yongquan
AU  - Shi Y
FAU - Li, Zhichao
AU  - Li Z
FAU - Fan, Daiming
AU  - Fan D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Butadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MGr1-antigen, human)
RN  - 0 (Nitriles)
RN  - 0 (Oxidants)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (U 0126)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/*genetics/metabolism
MH  - *Apoptosis
MH  - Blotting, Western
MH  - Butadienes/pharmacology
MH  - Cell Adhesion
MH  - Cell Movement
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Hydrogen Peroxide/pharmacology
MH  - Hypoxia/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors/metabolism
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*physiology
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*physiology
MH  - Nitriles/pharmacology
MH  - Oxidants/pharmacology
MH  - Phosphorylation
MH  - Promoter Regions, Genetic/genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Stomach Neoplasms/metabolism/*pathology
MH  - Tumor Cells, Cultured
EDAT- 2009/12/10 06:00
MHDA- 2010/07/21 06:00
CRDT- 2009/12/10 06:00
PHST- 2009/12/10 06:00 [entrez]
PHST- 2009/12/10 06:00 [pubmed]
PHST- 2010/07/21 06:00 [medline]
AID - 10.1002/ijc.25098 [doi]
PST - ppublish
SO  - Int J Cancer. 2010 Aug 15;127(4):820-9. doi: 10.1002/ijc.25098.