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Titolo:
Ganglioside G(D2) in small cell lung cancer cell lines: Enhancement of cell proliferation and mediation of apoptosis
Autore:
Yoshida, S; Fukumoto, S; Kawaguchi, H; Sato, S; Ueda, R; Furukawa, K;
Indirizzi:
Nagoya Univ, Sch Med, Dept Biochem 2, Showa Ku, Nagoya, Aichi 4660065, Japan Nagoya Univ Nagoya Aichi Japan 4660065 a Ku, Nagoya, Aichi 4660065, Japan Nagasaki Univ, Sch Dent, Dept Pediat Dent, Nagasaki 8528102, Japan Nagasaki Univ Nagasaki Japan 8528102 ediat Dent, Nagasaki 8528102, Japan Nagoya City Univ, Sch Med, Dept Internal Med 2, Nagoya, Aichi 4678601, Japan Nagoya City Univ Nagoya Aichi Japan 4678601 Nagoya, Aichi 4678601, Japan
Titolo Testata:
CANCER RESEARCH
fascicolo: 10, volume: 61, anno: 2001,
pagine: 4244 - 4252
SICI:
0008-5472(20010515)61:10<4244:GGISCL>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEURO-BLASTOMA CELLS; GM2 MONOCLONAL-ANTIBODY; HUMAN-MELANOMA; EXPRESSION CLONING; GD2 GANGLIOSIDE; SYNTHASE GENE; COMPLEX GANGLIOSIDES; MALIGNANT-MELANOMA; TARGET ANTIGEN; IN-VITRO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Furukawa, K Nagoya Univ, Sch Med, Dept Biochem 2, Showa Ku, 65 Tsurumai, Nagoya, Aichi4660065, Japan Nagoya Univ 65 Tsurumai Nagoya Aichi Japan 4660065 0065, Japan
Citazione:
S. Yoshida et al., "Ganglioside G(D2) in small cell lung cancer cell lines: Enhancement of cell proliferation and mediation of apoptosis", CANCER RES, 61(10), 2001, pp. 4244-4252

Abstract

Expression levels of gangliosides and glycosyltransferase genes responsible for their syntheses in human lung cancer cell lines and a normal bronchial epithelial cell line were analyzed. Both non-small cell lung cancers and small cell lung cancers (SCLCs) mainly expressed G(M2) and G(M1), whereas only SCLCs expressed b-series gangliosides, such as G(D2), G(D1b), and G(T1b). Accordingly, many SCLC cell lines showed up-regulation of the G(D3) synthase gene. Consequently, we introduced G(D3) synthase cDNA into a SCLC linewith low expression of b-series gangliosides and analyzed the effects of newly expressed gangliosides on tumor phenotypes. The transfectant cells expressing high levels of G(D2) and G(D3) exhibited markedly increased growth rates and strongly enhanced invasion activities. Addition of anti-G(D2) monoclonal antibodies into the culture medium of these cells resulted in the marked growth suppression of G(D2)-expressing cell lines with reduced activation levels of mitogen-activated protein kinases but not of nonexpressants,suggesting that G(D2) plays important roles in cell proliferation. Moreover, G(D2)-expressing cells treated with anti-G(D2) antibodies showed features of apoptotic cell death at 30 min after addition of antibodies, i.e., shrinkage of cytoplasm, binding of Annexin V, and staining with propidium iodide, followed by DNA fragmentation. This G(D2)-mediated apoptosis was associated with caspase-3 activation and partly inhibited by a caspase inhibitor,z-Val-Ala-Asp-fluoromethyl ketone. The finding that anti-G(D2) antibodies suppressed the cell growth and induced apoptosis of SCLC cells strongly suggested the usefulness of G(D2) as a target for the therapy of disastrous cancer, although the precise mechanisms for apoptosis remain to be clarified.

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Documento generato il 20/01/21 alle ore 12:10:04