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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0024623,
umls-concept:C0185117,
umls-concept:C0215848,
umls-concept:C0334227,
umls-concept:C1173384,
umls-concept:C1314939,
umls-concept:C1367780,
umls-concept:C1539696,
umls-concept:C1705231,
umls-concept:C1822686,
umls-concept:C2348110,
umls-concept:C2348977,
umls-concept:C2911684
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pubmed:issue |
1-2
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pubmed:dateCreated |
2007-8-9
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pubmed:abstractText |
Drug resistance is a major obstacle in the development of effective cancer therapy. It was reported that many chemotherapeutic drugs such as vincristine (VCR), a potent anti-tumor agent that associates with microtubules and disrupts the microtubular system, was found in acquisition of drug-resistance associated with an increase of HIF-1 expression via activating the NF-gammaB signal pathway. However, the multifactorial mechanism responsible for VCR increased HIF-1alpha expression remains to be fully elucidated. MGr1-Ag was previously reported by our laboratory as an upregulated protein in VCR-resistant cell lines SGC7901/VCR. In our study, detection of HIF-1 expression in SGC7901 cells and SGC7901/VCR cell or VCR-treated SGC7901cells showed that VCR could induce a significant expression of HIF-1alpha and VCR-resistant SGC7901/VCR cells had much higher expression of HIF-1alpha. Under nonhypoxic condition, VCR could enhance DNA binding activity and transcriptional activity of HIF-1alpha by 5.42- and 9.42-fold, respectively. Further study showed that forced expression of MGr1-Ag/37LRP upregulated HIF-1alpha protein expression and transcriptional activity in gastric cancer cell under nonhypoxic condition whereas siRNA targeting MGr1-Ag showed a markedly decreased VCR-induced HIF-1alpha expression and transcriptional activity (P < 0.05). SiRNA targeting FAK or inhibitors of phosphatidylinositol 3-kinase (PI3K) and MAPK could inhibit VCR-induced HIF-1alpha expression, suggesting FAK-PI3K and p42/44MAPK (Erk1/2) may be the major signaling molecules in MGr1-Ag/37LRP-induced HIF-1alpha expression and activity. These data support a model in which MGr1-Ag was a focal point for the convergence of VCR-mediated signaling events leading to HIF-1Alpha induction, thus revealing a novel aspect of HIF-1alpha regulation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/MGr1-antigen, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/PTK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Vincristine
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0300-8177
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pubmed:author |
pubmed-author:FanDaimingD,
pubmed-author:FengZ PZP,
pubmed-author:GuoChangcunC,
pubmed-author:HanShuangS,
pubmed-author:LiuLiliL,
pubmed-author:NingXiaoxuanX,
pubmed-author:ShiYongquanY,
pubmed-author:SunShirenS,
pubmed-author:VioMM,
pubmed-author:WuKaichunK,
pubmed-author:YinFangF
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pubmed:issnType |
Print
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pubmed:volume |
303
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
151-60
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17476462-Antigens, Neoplasm,
pubmed-meshheading:17476462-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:17476462-Blotting, Western,
pubmed-meshheading:17476462-Caspase 3,
pubmed-meshheading:17476462-Cell Hypoxia,
pubmed-meshheading:17476462-Focal Adhesion Kinase 1,
pubmed-meshheading:17476462-Humans,
pubmed-meshheading:17476462-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:17476462-Mitogen-Activated Protein Kinases,
pubmed-meshheading:17476462-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17476462-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:17476462-RNA, Messenger,
pubmed-meshheading:17476462-RNA, Small Interfering,
pubmed-meshheading:17476462-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:17476462-Signal Transduction,
pubmed-meshheading:17476462-Stomach Neoplasms,
pubmed-meshheading:17476462-Transcription, Genetic,
pubmed-meshheading:17476462-Tumor Cells, Cultured,
pubmed-meshheading:17476462-Vincristine
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pubmed:year |
2007
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pubmed:articleTitle |
Involvement of MGr1-Ag/37LRP in the vincristine-induced HIF-1 expression in gastric cancer cells.
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pubmed:affiliation |
State Key Laboratory of Cancer Biology, Institute of Digestive Diseases Xijing Hospital, Fourth Military Medical University, Xi'an, PR China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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