Source:http://linkedlifedata.com/resource/pubmed/id/10945642
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
15
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| pubmed:dateCreated |
2000-8-31
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| pubmed:abstractText |
We have shown recently that the multifunctional growth factor, scatter factor/hepatocyte growth factor (SF/HGF), and its receptor c-met enhance the malignancy of human glioblastoma through an autocrine stimulatory loop (R. Abounader et al., J. Natl. Cancer Inst., 91: 1548-1556, 1999). This report examines the effects of SF/HGF:c-met signaling on human glioma cell responses to DNA-damaging agents. Pretreating U373 human glioblastoma cells with recombinant SF/HGF partially abrogated their cytotoxic responses to gamma irradiation, cisplatin, camptothecin, Adriamycin, and Taxol in vitro. This cytoprotective effect of SF/HGF occurred at least in part through an inhibition of apoptosis, as evidenced by diminished terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling index and reduced DNA laddering. Anti-c-met U1/ribozyme gene transfer inhibited the ability of SF/HGF to protect against single-strand DNA breakage, DNA fragmentation, and glioblastoma cell death caused by DNA-damaging agents, demonstrating a requirement for c-met receptor function. Phosphorylation of the cell survival-promoting kinase Akt (protein kinase B) resulted from SF/HGF treatment of U373 cells, and both Akt phosphorylation and cell survival induced by SF/HGF were inhibited by phosphatidylinositol 3-kinase inhibitors but not by inhibitors of mitogen-activated protein kinase kinase or protein kinase C. Cytoprotection by SF/HGF in vitro was also inhibited by transient expression of dominant-negative Akt. Transgenic SF/HGF expression by intracranial 9L gliosarcomas reduced tumor cell sensitivity to gamma irradiation, confirming the cytoprotective effect of SF/HGF in vivo. These findings demonstrate that c-met receptor activation by SF/HGF protects certain glioblastoma cells from DNA-damaging agents by activating phosphoinositol 3-kinase-dependent and Akt-dependent antiapoptotic pathways.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-met,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Catalytic,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleoprotein, U1 Small Nuclear
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
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| pubmed:issn |
0008-5472
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
60
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
4277-83
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:10945642-Animals,
pubmed-meshheading:10945642-Apoptosis,
pubmed-meshheading:10945642-Gene Expression,
pubmed-meshheading:10945642-Gene Transfer Techniques,
pubmed-meshheading:10945642-Glioblastoma,
pubmed-meshheading:10945642-Gliosarcoma,
pubmed-meshheading:10945642-Hepatocyte Growth Factor,
pubmed-meshheading:10945642-Humans,
pubmed-meshheading:10945642-Male,
pubmed-meshheading:10945642-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:10945642-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10945642-Protein-Tyrosine Kinases,
pubmed-meshheading:10945642-Proto-Oncogene Proteins,
pubmed-meshheading:10945642-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:10945642-Proto-Oncogene Proteins c-met,
pubmed-meshheading:10945642-RNA, Catalytic,
pubmed-meshheading:10945642-Rats,
pubmed-meshheading:10945642-Rats, Inbred F344,
pubmed-meshheading:10945642-Recombinant Proteins,
pubmed-meshheading:10945642-Ribonucleoprotein, U1 Small Nuclear,
pubmed-meshheading:10945642-Signal Transduction,
pubmed-meshheading:10945642-Tumor Cells, Cultured
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| pubmed:year |
2000
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| pubmed:articleTitle |
Scatter factor/hepatocyte growth factor protects against cytotoxic death in human glioblastoma via phosphatidylinositol 3-kinase- and AKT-dependent pathways.
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| pubmed:affiliation |
Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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