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- Publisher Website: 10.1006/mthe.2000.0241
- Scopus: eid_2-s2.0-0034986068
- PMID: 11237673
- WOS: WOS:000167343800006
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Article: Specific down-regulation of HER-2/neu mediated by a chimeric U6 hammerhead ribozyme results in growth inhibition of human ovarian carcinoma
Title | Specific down-regulation of HER-2/neu mediated by a chimeric U6 hammerhead ribozyme results in growth inhibition of human ovarian carcinoma |
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Authors | |
Keywords | Gene therapy HER-2/neu ribozyme Ovarian cancer growth inhibition U6 RNA |
Issue Date | 2001 |
Citation | Molecular Therapy, 2001, v. 3 n. 2, p. 169-177 How to Cite? |
Abstract | The U6 expression system was explored for efficient expression of a ribozyme against the human proto-oncogene c-neu. A hammerhead ribozyme (neuRz) and the control mutant ribozyme (MRz) were targeted to cleave c-neu mRNA at the tyrosine kinase domain. In vitro cleavage showed that neuRz was very active while MRz was not. Near-maximal target cleavage observed at a low ribozyme:target ratio (0.1) suggests that neuRz has good activity and turnover capability under physiological conditions, i.e., <5 mM MgCI2 and 37°C. Chimeric U6 ribozyme was expressed at about 5 × 106 copies/cell at 48 h in the ovarian carcinoma cell line SKOV-3.ip1. Partial down-regulation of c-neu mRNA and protein was observed in a dose-dependent manner in cells transiently transfected with U6neuRz- but not with MRz-containing plasmid. Sorted transient transfectants demonstrated dramatic growth inhibition with the neuRz-expressing cells. Our results demonstrate that the U6 expression system is very efficient and suitable for the expression of a hammerhead ribozyme. Moreover, nonviral delivery of the neuRz-expressing plasmid resulted in specific down-regulation of c-neu and, subsequently, growth inhibition of ovarian cancer cells overexpressing c-neu. |
Persistent Identifier | http://hdl.handle.net/10722/194120 |
ISSN | 2023 Impact Factor: 12.1 2023 SCImago Journal Rankings: 3.736 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Lui, VWY | - |
dc.contributor.author | He, Y | - |
dc.contributor.author | Goyaland, K | - |
dc.contributor.author | Huang, L | - |
dc.date.accessioned | 2014-01-30T03:32:11Z | - |
dc.date.available | 2014-01-30T03:32:11Z | - |
dc.date.issued | 2001 | - |
dc.identifier.citation | Molecular Therapy, 2001, v. 3 n. 2, p. 169-177 | - |
dc.identifier.issn | 1525-0016 | - |
dc.identifier.uri | http://hdl.handle.net/10722/194120 | - |
dc.description.abstract | The U6 expression system was explored for efficient expression of a ribozyme against the human proto-oncogene c-neu. A hammerhead ribozyme (neuRz) and the control mutant ribozyme (MRz) were targeted to cleave c-neu mRNA at the tyrosine kinase domain. In vitro cleavage showed that neuRz was very active while MRz was not. Near-maximal target cleavage observed at a low ribozyme:target ratio (0.1) suggests that neuRz has good activity and turnover capability under physiological conditions, i.e., <5 mM MgCI2 and 37°C. Chimeric U6 ribozyme was expressed at about 5 × 106 copies/cell at 48 h in the ovarian carcinoma cell line SKOV-3.ip1. Partial down-regulation of c-neu mRNA and protein was observed in a dose-dependent manner in cells transiently transfected with U6neuRz- but not with MRz-containing plasmid. Sorted transient transfectants demonstrated dramatic growth inhibition with the neuRz-expressing cells. Our results demonstrate that the U6 expression system is very efficient and suitable for the expression of a hammerhead ribozyme. Moreover, nonviral delivery of the neuRz-expressing plasmid resulted in specific down-regulation of c-neu and, subsequently, growth inhibition of ovarian cancer cells overexpressing c-neu. | - |
dc.language | eng | - |
dc.relation.ispartof | Molecular Therapy | - |
dc.subject | Gene therapy | - |
dc.subject | HER-2/neu ribozyme | - |
dc.subject | Ovarian cancer growth inhibition | - |
dc.subject | U6 RNA | - |
dc.title | Specific down-regulation of HER-2/neu mediated by a chimeric U6 hammerhead ribozyme results in growth inhibition of human ovarian carcinoma | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1006/mthe.2000.0241 | - |
dc.identifier.pmid | 11237673 | - |
dc.identifier.scopus | eid_2-s2.0-0034986068 | - |
dc.identifier.volume | 3 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 169 | - |
dc.identifier.epage | 177 | - |
dc.identifier.isi | WOS:000167343800006 | - |
dc.identifier.issnl | 1525-0016 | - |