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Titolo:
Transformation-defective adenovirus 5 E1A mutants exhibit antioncogenic properties in human BLM melanoma cells
Autore:
Dickopp, A; Esche, H; Swart, G; Seeber, S; Kirch, HC; Opalka, B;
Indirizzi:
Univ Essen Gesamthsch, Sch Med, Inst Mol Biol Canc Res, D-45147 Essen, Germany Univ Essen Gesamthsch Essen Germany D-45147 Res, D-45147 Essen, Germany Univ Essen Gesamthsch, Sch Med, Dept Internal Med Canc Res, D-45147 Essen,Germany Univ Essen Gesamthsch Essen Germany D-45147 c Res, D-45147 Essen,Germany Univ Nijmegen, Dept Biochem, Nijmegen, Netherlands Univ Nijmegen Nijmegen Netherlands Dept Biochem, Nijmegen, Netherlands
Titolo Testata:
CANCER GENE THERAPY
fascicolo: 7, volume: 7, anno: 2000,
pagine: 1043 - 1050
SICI:
0929-1903(200007)7:7<1043:TA5EME>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN TUMOR-CELLS; GENE-PRODUCTS; TRANSCRIPTIONAL REGULATION; CELLULAR PHOSPHOPROTEIN; MEDIATED TRANSFORMATION; NEGATIVE MODULATION; FUNCTIONAL DOMAINS; CARCINOMA-CELLS; IN-VIVO; EXPRESSION;
Keywords:
E1A; BLM cells; melanoma; gene therapy; tumor suppression;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Kirch, HC Univ Essen Gesamthsch, Sch Med, Inst Mol Biol Canc Res, Hufelandstr 55, D-45147 Essen, Germany Univ Essen Gesamthsch Hufelandstr 55 Essen Germany D-45147 many
Citazione:
A. Dickopp et al., "Transformation-defective adenovirus 5 E1A mutants exhibit antioncogenic properties in human BLM melanoma cells", CANC GENE T, 7(7), 2000, pp. 1043-1050

Abstract

Adenoviral E1A proteins exhibit a strong tumor-suppressive activity in human tumor cells. However, E1A is capable of transforming rodent and human cells in cooperation with other oncoproteins, such as activated RAS. Thus, the therapeutic use of wild-type E1A harbors the principal risk of enhancing tumor malignancy. This prompted us to construct E1A 13S cDNA-derived mutants that were unable to transform baby mouse kidney cells in cooperation withE1B and to test their tumor-suppressive activity in BLM human melanoma cells. Anchorage-independent growth in soft agar was reduced for those cell lines expressing the E1A(delCR2) mutant, which lacks the entire conserved region 2 (CR2) sequences, or for cells expressing the E1A(CR3Ex2) mutant, which contains CR3 plus exon 2 sequences. In contrast, cell lines expressing the entire E1A wild-type (E1A(WT)) or only the exon 2 sequences (E1A(Ex2)) grew like the parental BLM cells. Moreover, inoculation of nude mice with BLMcells or cells expressing E1A(Ex2) revealed large tumors after 2 weeks. Incontrast, tumors derived from E1A(delCR2)- or E1A(CR3Ex2)-expressing cellsexhibited a substantial delay in tumor growth accompanied by a loss of E1Aexpression in the outgrown tumors. Cell lines expressing E1A(WT) showed anintermediate phenotype. Thus, expression of CR3 plus exon 2 sequences is sufficient to enhance both the antioncogenic properties and the therapeutic safety of E1A in our system.

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Documento generato il 26/09/20 alle ore 11:01:05