PMID- 21725207
OWN - NLM
STAT- MEDLINE
DCOM- 20120119
LR  - 20200930
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Linking)
VI  - 12
IP  - 6
DP  - 2011 Sep 15
TI  - Interferon-alpha sensitizes human gastric cancer cells to TRAIL-induced apoptosis via 
      activation of the c-CBL-dependent MAPK/ERK pathway.
PG  - 494-502
LID - 10.4161/cbt.12.6.15973 [doi]
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of 
      the tumor necrosis factor family that induces apoptosis in cancer cells. However, 
      gastric cancer cells are insensitive to TRAIL. In the present study, we show that 
      pretreatment with IFN-alpha enhanced TRAIL-induced apoptosis of gastric cancer MGC803 
      cells. IFN-alpha up-regulated death receptor 5 (DR5) expression and down-regulated 
      survivin expression. Furthermore, extracellular-regulated protein kinase (ERK1/2) 
      activation was induced by IFN-alpha, and a combination of IFN-alpha and TRAIL led to 
      further activation of ERK1/2. Inhibition of the MAPK/ERK signaling pathway 
      partially reversed apoptosis, as well as the expression patterns of DR5 and 
      survivin. Moreover, the expression of the c-casitas B-lineage lymphoma (c-Cbl) 
      family was down-regulated by IFN-alpha. Transfection of c-Cbl suppressed 
      IFN-alpha-induced ERK activation. These results indicate that IFN-alpha enhances 
      TRAIL-induced apoptosis in gastric cancer cells at least partially via 
      downregulation of c-Cbl, and subsequent up-regulation of the MAPK/ERK pathway.
FAU - Qu, Jinglei
AU  - Qu J
AD  - China Medical University, Heping District, Shenyang City. qu_xiujuan@hotmail.com
FAU - Zhao, Mingfang
AU  - Zhao M
FAU - Teng, Yuee
AU  - Teng Y
FAU - Zhang, Ye
AU  - Zhang Y
FAU - Hou, Kezuo
AU  - Hou K
FAU - Jiang, Youhong
AU  - Jiang Y
FAU - Yang, Xianghong
AU  - Yang X
FAU - Shang, Hong
AU  - Shang H
FAU - Qu, Xiujuan
AU  - Qu X
FAU - Liu, Yunpeng
AU  - Liu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110915
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Interferon-alpha)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 6.3.2.- (CBL protein, human)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Caspases/metabolism
MH  - Cell Line, Tumor
MH  - Drug Synergism
MH  - Enzyme Activation
MH  - Gene Expression
MH  - Humans
MH  - Interferon-alpha/*pharmacology
MH  - *MAP Kinase Signaling System
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-cbl/genetics/*metabolism
MH  - Stomach Neoplasms
MH  - TNF-Related Apoptosis-Inducing Ligand/*pharmacology
EDAT- 2011/07/05 06:00
MHDA- 2012/01/20 06:00
CRDT- 2011/07/05 06:00
PHST- 2011/07/05 06:00 [entrez]
PHST- 2011/07/05 06:00 [pubmed]
PHST- 2012/01/20 06:00 [medline]
AID - 15973 [pii]
AID - 10.4161/cbt.12.6.15973 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2011 Sep 15;12(6):494-502. doi: 10.4161/cbt.12.6.15973. Epub 
      2011 Sep 15.