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PubMed:10491431 JSONTXT

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PubMed_Structured_Abstracts

Id Subject Object Predicate Lexical cue
T1 163-842 BACKGROUND denotes Expression of scatter factor (SF), also known as hepatocyte growth factor (HGF), and its receptor, c-met, is often associated with malignant progression of human tumors, including gliomas. Overexpression of SF/HGF in experimental gliomas enhances tumorigenicity and tumor-associated angiogenesis (i.e., growth of new blood vessels). However, the role of endogenous SF/HGF or c-met expression in the malignant progression of gliomas has not been examined directly. In this study, we tested the hypothesis that human glioblastomas can be SF/HGF-c-met dependent and that a reduction in endogenous SF/HGF or c-met expression can lead to inhibition of tumor growth and tumorigenicity.
T2 852-1432 METHODS denotes Expression of the SF/HGF and c-met genes was inhibited by transfecting glioblastoma cells with chimeric transgenes consisting of U1 small nuclear RNA, a hammerhead ribozyme, and antisense sequences. The effects of reduced SF/HGF and c-met expression on 1) SF/HGF-dependent induction of immediate early genes (c-fos and c-jun), indicative of signal transduction; 2) anchorage-independent colony formation (clonogenicity), an in vitro correlate of solid tumor malignancy; and 3) intracranial tumor formation in immunodeficient mice were quantified. Statistical tests were two-sided.
T3 1442-1956 RESULTS denotes Introduction of the transgenes into glioblastoma cells reduced expression of the SF/HGF and c-met genes to as little as 2% of control cell levels. Reduction in c-met expression specifically inhibited SF/HGF-dependent signal transduction (P<.01). Inhibition of SF/HGF or c-met expression in glioblastoma cells possessing an SF/HGF-c-met autocrine loop reduced tumor cell clonogenicity (P =.005 for SF/HGF and P=.009 for c-met) and substantially inhibited tumorigenicity (P<.0001) and tumor growth in vivo (P<.0001).
T4 1970-2293 CONCLUSIONS denotes To our knowledge, this is the first successful inhibition of SF/HGF and c-met expression in a tumor model directly demonstrating a role for endogenous SF/HGF and c-met in human glioblastoma. Our results suggest that targeting the SF/HGF-c-met signaling pathway may be an important approach in controlling tumor progression.

PubmedHPO

Id Subject Object Predicate Lexical cue
T1 325-331 HP_0002664 denotes tumors
T2 343-350 HP_0009733 denotes gliomas
T3 393-400 HP_0009733 denotes gliomas
T4 429-434 HP_0002664 denotes tumor
T5 587-594 HP_0009733 denotes gliomas
T6 678-691 HP_0100843 denotes glioblastomas
T7 810-815 HP_0002664 denotes tumor

DisGeNET5_gene_disease

Id Subject Object Predicate Lexical cue
10491431-10#61#63#gene3082 2031-2033 gene3082 denotes SF
10491431-10#64#67#gene3082 2034-2037 gene3082 denotes HGF
10491431-10#151#153#gene3082 2121-2123 gene3082 denotes SF
10491431-10#154#157#gene3082 2124-2127 gene3082 denotes HGF
10491431-10#177#189#diseaseC0017636 2147-2159 diseaseC0017636 denotes glioblastoma
10491431-11#42#45#gene3082 2203-2206 gene3082 denotes HGF
10491431-11#48#51#diseaseC0268621 2209-2212 diseaseC0268621 denotes met
10491431-11#114#131#diseaseC0178874 2275-2292 diseaseC0178874 denotes tumor progression
10491431-3#35#38#gene3082 531-534 gene3082 denotes HGF
10491431-3#91#98#diseaseC0017638 587-594 diseaseC0017638 denotes gliomas
10491431-6#26#29#gene3082 1077-1080 gene3082 denotes HGF
10491431-6#60#63#gene3082 1111-1114 gene3082 denotes HGF
10491431-6#247#258#diseaseC0280100 1298-1309 diseaseC0280100 denotes solid tumor
10491431-6#310#325#diseaseC0021051 1361-1376 diseaseC0021051 denotes immunodeficient
10491431-6#247#258#diseaseC0280100 1298-1309 diseaseC0280100 denotes solid tumor
10491431-6#310#325#diseaseC0021051 1361-1376 diseaseC0021051 denotes immunodeficient
61#63#gene3082177#189#diseaseC0017636 10491431-10#61#63#gene3082 10491431-10#177#189#diseaseC0017636 associated_with SF,glioblastoma
64#67#gene3082177#189#diseaseC0017636 10491431-10#64#67#gene3082 10491431-10#177#189#diseaseC0017636 associated_with HGF,glioblastoma
151#153#gene3082177#189#diseaseC0017636 10491431-10#151#153#gene3082 10491431-10#177#189#diseaseC0017636 associated_with SF,glioblastoma
154#157#gene3082177#189#diseaseC0017636 10491431-10#154#157#gene3082 10491431-10#177#189#diseaseC0017636 associated_with HGF,glioblastoma
42#45#gene308248#51#diseaseC0268621 10491431-11#42#45#gene3082 10491431-11#48#51#diseaseC0268621 associated_with HGF,met
42#45#gene3082114#131#diseaseC0178874 10491431-11#42#45#gene3082 10491431-11#114#131#diseaseC0178874 associated_with HGF,tumor progression
35#38#gene308291#98#diseaseC0017638 10491431-3#35#38#gene3082 10491431-3#91#98#diseaseC0017638 associated_with HGF,gliomas
26#29#gene3082247#258#diseaseC0280100 10491431-6#26#29#gene3082 10491431-6#247#258#diseaseC0280100 associated_with HGF,solid tumor
26#29#gene3082310#325#diseaseC0021051 10491431-6#26#29#gene3082 10491431-6#310#325#diseaseC0021051 associated_with HGF,immunodeficient
26#29#gene3082247#258#diseaseC0280100 10491431-6#26#29#gene3082 10491431-6#247#258#diseaseC0280100 associated_with HGF,solid tumor
26#29#gene3082310#325#diseaseC0021051 10491431-6#26#29#gene3082 10491431-6#310#325#diseaseC0021051 associated_with HGF,immunodeficient
60#63#gene3082247#258#diseaseC0280100 10491431-6#60#63#gene3082 10491431-6#247#258#diseaseC0280100 associated_with HGF,solid tumor
60#63#gene3082310#325#diseaseC0021051 10491431-6#60#63#gene3082 10491431-6#310#325#diseaseC0021051 associated_with HGF,immunodeficient
60#63#gene3082247#258#diseaseC0280100 10491431-6#60#63#gene3082 10491431-6#247#258#diseaseC0280100 associated_with HGF,solid tumor
60#63#gene3082310#325#diseaseC0021051 10491431-6#60#63#gene3082 10491431-6#310#325#diseaseC0021051 associated_with HGF,immunodeficient

DisGeNET

Id Subject Object Predicate Lexical cue
T0 177-191 gene:3082 denotes scatter factor
T1 343-350 disease:C0017638 denotes gliomas
T2 193-195 gene:3082 denotes SF
T3 343-350 disease:C0017638 denotes gliomas
T4 212-236 gene:3082 denotes hepatocyte growth factor
T5 343-350 disease:C0017638 denotes gliomas
T6 238-241 gene:3082 denotes HGF
T7 343-350 disease:C0017638 denotes gliomas
R1 T0 T1 associated_with scatter factor,gliomas
R2 T2 T3 associated_with SF,gliomas
R3 T4 T5 associated_with hepatocyte growth factor,gliomas
R4 T6 T7 associated_with HGF,gliomas