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Titolo:
Reduction of c-myc expression by an antisense approach under Cre/loxP switching induces apoptosis in human liver cancer cells
Autore:
Ebinuma, H; Saito, H; Kosuga, M; Wakabayashi, K; Saito, Y; Takagi, T; Nakamoto, N; Okuyama, T; Ishii, H;
Indirizzi:
Keio Univ, Sch Med, Dept Int Med, Shinjuku Ku, Tokyo 160, Japan Keio UnivTokyo Japan 160 d, Dept Int Med, Shinjuku Ku, Tokyo 160, Japan Natl Childrens Med Res Ctr, Dept Genet, Tokyo, Japan Natl Childrens Med Res Ctr Tokyo Japan es Ctr, Dept Genet, Tokyo, Japan
Titolo Testata:
JOURNAL OF CELLULAR PHYSIOLOGY
fascicolo: 1, volume: 188, anno: 2001,
pagine: 56 - 66
SICI:
0021-9541(200107)188:1<56:ROCEBA>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN HEPATOCELLULAR-CARCINOMA; EFFICIENT GENE ACTIVATION; HUMAN HEPATOMA-CELLS; HCC-T; PROSTATE-CANCER; CRE RECOMBINASE; CELLULAR UPTAKE; HEPATITIS-B; HL-60 CELLS; P53 GENE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Saito, H Keio Univ, Sch Med, Dept Int Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 160,Japan Keio Univ 35 Shinanomachi Tokyo Japan 160 machi, Tokyo 160,Japan
Citazione:
H. Ebinuma et al., "Reduction of c-myc expression by an antisense approach under Cre/loxP switching induces apoptosis in human liver cancer cells", J CELL PHYS, 188(1), 2001, pp. 56-66

Abstract

c-Myc has been documented to be both a positive and a negative signal for the induction of apoptosis. It is well known that overexpression of the c-myc gene induces apoptosis of normal cells, but the result of a reduction inits expression is not fully understood. We examined whether a reduction inc-myc expression would induce apoptosis in human liver cancer cells. Specifically, antisense and sense oligodeoxynucleotides (oligos) against the human c-myc mRNA were synthesized, mixed with a liposome reagent at various ratios, and were applied to the liver cancer-derived cell lines, HCC-T, HepG2, and PLC/PRF/5. To exclude effects resulting from using oligos, plasmid vectors expressing the full-length c-myc cDNA in both sense and antisense orientations under the control of the Cre/IoxP system were generated. Monoclonal cell lines including these plasmid vectors were produced and Cre was supplied by adenovirus infection. Apoptosis was determined morphologically andc-Myc and Bcl-2 expression was examined by Western blotting. The antisensemyc significantly inhibited the proliferation of the cells within two days, while neither the liposome reagent alone nor sense myc did so. Most of the cells were rounded up by the antisense-treatment and nuclear fragmentation and DNA ladder formation were detected after two days in antisense c-myc-treated cells. Antisense c-myc largely reduced c-Myc and partially Bcl-2 expression; overexpression of Bcl-2 partially rescued from apoptosis in HCC-Tand HepG2 cells. These results suggest that the massive reduction in c-mycmRNA induces apoptosis in liver cancer cell lines and consequent decrease in Bcl-2 enhances the cell death. c-Myc reduction under the Cre/IoxP switching system may be a useful tool for the clarification of c-myc-related cellular mechanisms in differentiation and proliferation. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 07:29:55