PubMed:10491431
Annnotations
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 |