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Titolo:
Improved safety through tamoxifen-regulated induction of cytotoxic genes delivered by Ad vectors for cancer gene therapy
Autore:
Putzer, BM; Stiewe, T; Crespo, F; Esche, H;
Indirizzi:
Univ Essen Gesamthsch, Sch Med, Inst Mol Biol Canc Res, D-45122 Essen, Germany Univ Essen Gesamthsch Essen Germany D-45122 Res, D-45122 Essen, Germany
Titolo Testata:
GENE THERAPY
fascicolo: 15, volume: 7, anno: 2000,
pagine: 1317 - 1325
SICI:
0969-7128(200008)7:15<1317:ISTTIO>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARCINOMA CELL-LINES; EXPRESSION IN-VIVO; MAMMALIAN-CELLS; TRANSGENE EXPRESSION; ADENOVIRAL VECTORS; GROWTH SUPPRESSION; TUMOR-REGRESSION; S-PHASE; APOPTOSIS; PROTEIN;
Keywords:
gene therapy; adenovirus; apoptosis; E2F1; ER-fusion protein; cancer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Putzer, BM Univ Essen Gesamthsch, Sch Med, Inst Mol Biol Canc Res, Hufelandstr 55, D-45122 Essen, Germany Univ Essen Gesamthsch Hufelandstr 55 EssenGermany D-45122 any
Citazione:
B.M. Putzer et al., "Improved safety through tamoxifen-regulated induction of cytotoxic genes delivered by Ad vectors for cancer gene therapy", GENE THER, 7(15), 2000, pp. 1317-1325

Abstract

The transfer of pro-apoptotic genes to tumors is one of the most promisingstrategies for anticancer gene therapy. However, the use of potentially toxic genes, such as tumor suppressor genes or apoptotic genes, needs controllable transgene activation. To achieve regulation of the transgene at a desired time, we developed an adenovirus (Ad) vector in which the apoptotic activity of the target gene has been made 4-OHT-dependent by fusion to the ligand binding-domain of the estrogen receptor (ER). For evaluation of the system in human tumor cells, we used the E2F1 gene which encodes a transcription factor that triggers massive apoptosis in several human cancers. AdER-E2F1 expressed high levels of transgene over at least I week. Upon activation of E2F1 by the ligand 4-hydroxy-tamoxifen (4-OHT) the ER-E2F1 fusion protein correctly translocated from the cytosol to the nucleus, transactivated E2F-dependent promoters, and rapidly induced substantial E2F1-related toxicity. Finally, experiments in nude mice showed tightly regulated tumor growth suppression in vivo. Taken together our system represents a powerful approach for tight regulation and rapid induction of cytotoxicity as the major criteria for safe gene delivery.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 06:52:39