PMID- 19123465
OWN - NLM
STAT- MEDLINE
DCOM- 20090303
LR  - 20160303
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 124
IP  - 7
DP  - 2009 Apr 1
TI  - Hypoxia-mediated up-regulation of MGr1-Ag/37LRP in gastric cancers occurs via 
      hypoxia-inducible-factor 1-dependent mechanism and contributes to drug 
      resistance.
PG  - 1707-15
LID - 10.1002/ijc.24135 [doi]
AB  - Our previous study demonstrated hypoxia-inducible factor-1(HIF-1) could prompt 
      multidrug resistance (MDR) phenotype and MGr1-Ag/37LRP, a novel drug-resistance 
      protein was reported by our labortary, associated with multidrug resistance in 
      gastric cancer. Given this association, we hypothesized that MGr1-Ag/37LRP 
      contributed to HIF-1-dependent hypoxia-induced MDR phenotype. Initial experiments 
      revealed that blocking MGr1-Ag/37LRP expression by siRNA in gastric cancer cells 
      effectively reversed multidrug resistance phenotype induced by hypoxia. 
      Subsequent analysis of MGr1-Ag/37LRP mRNA and protein in gastric cancer cells 
      revealed a time-dependent manner increase with hypoxia. While the up-regulation 
      of MGr1-Ag/37LRP was abolished by HIF-1 inhibition with siRNA. Studies using 
      luciferase promoter constructs revealed a significant increase in activity in 
      cells subject to hypoxia and such hypoxia inducibility was lost in cells 
      co-transfected siRNA targeting HIF-1. Analysis of the MGr1-Ag/37LRP promoter 
      revealed several potential binding sites for HIF-1. Electrophoretic mobility 
      shift assay and chromatin immunoprecipitation demonstrated a functional HIF-1 
      binding site within MGr1-Ag/37LRP gene regulatory sequence located at -16 to -11 
      relative to the transcriptional initiation point. These observations demonstrate 
      that MGr1-Ag/37LRP is actively engaged by hypoxia and represent a novel HIF-1 
      target. Such results suggest hypoxia-elicited MGr1-Ag/37LRP expression as a 
      pathway for resistance of gastric cancer to chemotherapeutics.
FAU - Liu, Lili
AU  - Liu L
AD  - State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing 
      Hospital, Fourth Military Medical University, Xi'an, China.
FAU - Sun, Li
AU  - Sun L
FAU - Zhang, Hongbo
AU  - Zhang H
FAU - Li, Zhichao
AU  - Li Z
FAU - Ning, Xiaoxuan
AU  - Ning X
FAU - Shi, Yongquan
AU  - Shi Y
FAU - Guo, Changcun
AU  - Guo C
FAU - Han, Shuang
AU  - Han S
FAU - Wu, Kaichun
AU  - Wu K
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 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MGr1-antigen, human)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Adenocarcinoma/genetics/*metabolism
MH  - Animals
MH  - Antigens, Neoplasm/genetics/*metabolism
MH  - Blotting, Western
MH  - Cell Hypoxia/*physiology
MH  - Drug Resistance, Neoplasm/*physiology
MH  - Electrophoretic Mobility Shift Assay
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Immunoprecipitation
MH  - Mice
MH  - RNA, Small Interfering
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stomach Neoplasms/genetics/*metabolism
MH  - Up-Regulation
EDAT- 2009/01/07 09:00
MHDA- 2009/03/04 09:00
CRDT- 2009/01/07 09:00
PHST- 2009/01/07 09:00 [entrez]
PHST- 2009/01/07 09:00 [pubmed]
PHST- 2009/03/04 09:00 [medline]
AID - 10.1002/ijc.24135 [doi]
PST - ppublish
SO  - Int J Cancer. 2009 Apr 1;124(7):1707-15. doi: 10.1002/ijc.24135.