PubMed:15264243
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/15264243","sourcedb":"PubMed","sourceid":"15264243","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/15264243","text":"Targeting the HGF/SF receptor c-met using a hammerhead ribozyme transgene reduces in vitro invasion and migration in prostate cancer cells.\nBACKGROUND: Hepatocyte growth factor scatter factor (HGF/SF) elicits a number of biological activities including invasion and migration through activation of its tyrosine kinase receptor c-Met. Over expression of c-Met has been implicated in prostate cancer development and progression. This study examined the effect of a ribozyme transgene, designed to inhibit human c-Met expression, and its impact on in vitro invasion and migration in prostate cancer.\nMETHODS: A transgene (Met 560) consisting of U1 snRNA, hammerhead ribozyme, and antisense was cloned into a modified pZeoU1-EcoSpe vector and transfected into DU-145 cells. The effect of HGF/SF was tested on prostate cancer cells whose expression of c-Met had been blocked by way of a ribozyme transgene.\nRESULTS: Met 560 stable transfectants (DU-145(+/+)) manifested a complete loss of c-Met expression at mRNA and protein levels. In contrast, control plasmid (DU-145(+/-)) and wild-type DU-145 cells (DU-145(-/-)) had similar levels of c-Met expression. HGF/SF significantly increased the in vitro invasiveness (mean 47.71 +/- SE 7.75; P \u003c 0.01 vs. control 24.14 +/- 1.34), and migration (mean 48.44 +/- SE 3.51; P \u003c 0.01 vs. control 22.95 +/- 1.47) of DU-145(-/-) cells, respectively. Similarly, HGF/SF also increased the invasion (62.33 +/- 6.34; P \u003c 0.001 vs. control 24.5 +/- 2.35) and migration (46.14 +/- 2.26; P \u003c 0.01 vs. control 21.82 +/- 1.62) of DU-145(+/-) cells. In contrast, DU-145(+/+) cells had lost its response to HGF/SF induced invasion (22.33 +/- 2.08; P \u003e 0.05 vs. control 23.5 +/- 2.11) and migration (24.12 +/- 0.86; P \u003e 0.05 vs. control 23.27 +/- 0.81).\nCONCLUSIONS: Targeting the HGF/SF receptor by way of a hammerhead ribozyme encoding antisense to c-Met, is an effective method to reduce the invasive or migration potential in prostate cancer, and may have important therapeutic implications.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":784,"end":787},"obj":"gene:3569"},{"id":"T1","span":{"begin":805,"end":820},"obj":"disease:C0376358"},{"id":"T2","span":{"begin":784,"end":787},"obj":"gene:3569"},{"id":"T3","span":{"begin":805,"end":820},"obj":"disease:C0600139"},{"id":"T4","span":{"begin":784,"end":787},"obj":"gene:6654"},{"id":"T5","span":{"begin":805,"end":820},"obj":"disease:C0376358"},{"id":"T6","span":{"begin":784,"end":787},"obj":"gene:6654"},{"id":"T7","span":{"begin":805,"end":820},"obj":"disease:C0600139"},{"id":"T8","span":{"begin":784,"end":787},"obj":"gene:3082"},{"id":"T9","span":{"begin":805,"end":820},"obj":"disease:C0376358"},{"id":"T10","span":{"begin":784,"end":787},"obj":"gene:3082"},{"id":"T11","span":{"begin":805,"end":820},"obj":"disease:C0600139"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"},{"subj":"T4","pred":"source","obj":"DisGeNET"},{"subj":"T5","pred":"source","obj":"DisGeNET"},{"subj":"T6","pred":"source","obj":"DisGeNET"},{"subj":"T7","pred":"source","obj":"DisGeNET"},{"subj":"T8","pred":"source","obj":"DisGeNET"},{"subj":"T9","pred":"source","obj":"DisGeNET"},{"subj":"T10","pred":"source","obj":"DisGeNET"},{"subj":"T11","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"15264243-0#14#29#gene4233","span":{"begin":14,"end":29},"obj":"gene4233"},{"id":"15264243-0#117#132#diseaseC0376358","span":{"begin":117,"end":132},"obj":"diseaseC0376358"},{"id":"15264243-0#117#132#diseaseC0600139","span":{"begin":117,"end":132},"obj":"diseaseC0600139"},{"id":"15264243-5#14#17#gene3082","span":{"begin":784,"end":787},"obj":"gene3082"},{"id":"15264243-5#35#50#diseaseC0376358","span":{"begin":805,"end":820},"obj":"diseaseC0376358"},{"id":"15264243-5#35#50#diseaseC0600139","span":{"begin":805,"end":820},"obj":"diseaseC0600139"}],"relations":[{"id":"14#29#gene4233117#132#diseaseC0376358","pred":"associated_with","subj":"15264243-0#14#29#gene4233","obj":"15264243-0#117#132#diseaseC0376358"},{"id":"14#29#gene4233117#132#diseaseC0600139","pred":"associated_with","subj":"15264243-0#14#29#gene4233","obj":"15264243-0#117#132#diseaseC0600139"},{"id":"14#17#gene308235#50#diseaseC0376358","pred":"associated_with","subj":"15264243-5#14#17#gene3082","obj":"15264243-5#35#50#diseaseC0376358"},{"id":"14#17#gene308235#50#diseaseC0600139","pred":"associated_with","subj":"15264243-5#14#17#gene3082","obj":"15264243-5#35#50#diseaseC0600139"}],"attributes":[{"subj":"15264243-0#14#29#gene4233","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15264243-0#117#132#diseaseC0376358","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15264243-0#117#132#diseaseC0600139","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15264243-5#14#17#gene3082","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15264243-5#35#50#diseaseC0376358","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15264243-5#35#50#diseaseC0600139","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":152,"end":596},"obj":"BACKGROUND"},{"id":"T2","span":{"begin":606,"end":901},"obj":"METHODS"},{"id":"T3","span":{"begin":911,"end":1776},"obj":"RESULTS"},{"id":"T4","span":{"begin":1790,"end":2018},"obj":"CONCLUSIONS"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T2","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T3","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T4","pred":"source","obj":"PubMed_Structured_Abstracts"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#93aeec","default":true},{"id":"DisGeNET5_gene_disease","color":"#c8ec93"},{"id":"PubMed_Structured_Abstracts","color":"#ec93e2"}]}]}}