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Titolo:
Specific down-regulation of HER-2/neu mediated by a chimeric U6 hammerheadribozyme results in growth inhibition of human ovarian carcinoma
Autore:
Lui, VWY; He, YK; Goyal, K; Huang, L;
Indirizzi:
Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 cogenet, Pittsburgh, PA 15213 USA Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA Univ Pittsburgh Pittsburgh PA USA 15261 armacol, Pittsburgh, PA 15261 USA Univ Pittsburgh, Sch Med, Dept Dermatol, Pittsburgh, PA 15261 USA Univ Pittsburgh Pittsburgh PA USA 15261 ermatol, Pittsburgh, PA 15261 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 2, volume: 3, anno: 2001,
pagine: 169 - 177
SICI:
1525-0016(200102)3:2<169:SDOHMB>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-BREAST-CANCER; IN-VIVO; GENE-TRANSFER; PROTO-ONCOGENE; CELL-LINES; HELIX-I; RNA; EXPRESSION; ANTISENSE; ADENOCARCINOMA;
Keywords:
HER-2/neu ribozyme; ovarian cancer growth inhibition; U6 RNA; gene therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Huang, L Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 Pittsburgh, PA 15213 USA
Citazione:
V.W.Y. Lui et al., "Specific down-regulation of HER-2/neu mediated by a chimeric U6 hammerheadribozyme results in growth inhibition of human ovarian carcinoma", MOL THER, 3(2), 2001, pp. 169-177

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 MgCl2 and 37<degrees>C. Chimeric U6 ribozyme was expressed at about 5 x 10(6) copies/cell at 48 h in the ovarian carcinoma cell line SKOV-3.ip1. Partial downregulation 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/02/20 alle ore 13:58:05