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Titolo:
Mutations in the mitotic check point gene, MAD1L1, in human cancers
Autore:
Tsukasaki, K; Miller, CW; Greenspun, E; Eshaghian, S; Kawabata, H; Fujimoto, T; Tomonaga, M; Sawyers, C; Said, JW; Koeffler, HP;
Indirizzi:
Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Div Hematol Oncol, Los Angeles, CA 90048 USA Univ Calif Los Angeles Los Angeles CA USA 90048 Los Angeles, CA 90048 USA Nagasaki Univ, Sch Med, Atom Bomb Dis Inst, Dept Hematol, Nagasaki 852, Japan Nagasaki Univ Nagasaki Japan 852 Inst, Dept Hematol, Nagasaki 852, Japan Univ Calif Los Angeles, Sch Med, Hlth Sci Ctr, Dept Med, Los Angeles, CA 90048 USA Univ Calif Los Angeles Los Angeles CA USA 90048 Los Angeles, CA 90048 USA Univ Calif Los Angeles, Sch Med, Hlth Sci Ctr, Dept Pathol, Los Angeles, CA 90048 USA Univ Calif Los Angeles Los Angeles CA USA 90048 Los Angeles, CA 90048 USA
Titolo Testata:
ONCOGENE
fascicolo: 25, volume: 20, anno: 2001,
pagine: 3301 - 3305
SICI:
0950-9232(20010531)20:25<3301:MITMCP>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LUNG CANCERS; VIRUS TYPE-I; SPINDLE CHECKPOINT; INSTABILITY; LYMPHOMA; CELLS; FRESH;
Keywords:
MAD1L1; mitotic checkpoint; chromosomal instability; prostate cancer; breast cancer; adult T-cell leukemia/lymphoma;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Tsukasaki, K Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Div Hematol Oncol, Los Angeles, CA 90048 USA Univ Calif Los Angeles Los Angeles CA USA 90048 CA 90048 USA
Citazione:
K. Tsukasaki et al., "Mutations in the mitotic check point gene, MAD1L1, in human cancers", ONCOGENE, 20(25), 2001, pp. 3301-3305

Abstract

Aneuploidy is a characteristic of the majority of human cancers, and recent studies suggest that defects of mitotic checkpoints play a role in carcinogenesis. MAD1L1 is a checkpoint gene, and its dysfunction is associated with chromosomal instability. Rare mutations of this gene have been reported in colon and lung cancers. We examined a total of 44 cell lines (hematopoietic, prostate, osteosarcoma, breast, glioblastoma and lung) and 133 fresh cancer cells (hematopoietic, prostate, breast and glioblastoma) for alterations of MAD1L1 by RT-PCR-SSCP and nucleotide sequencing. Eight mutations consisting of missense, nonsense and frameshift mutations were found, togetherwith a number of nucleotide polymorphisms. All the alterations in cell lines were heterozygous, Frequency of mutations was relatively high in prostate cancer (2/7 cell lines and 2/33 tumor specimens). We placed a mutant truncated MAD1L1, found in a lymphoma sample, into HOS, Ht161 and SJSA cell lines and found that it was less inhibitory than wild type MAD1L1 at decreasing cell proliferation. Go-expression experiments showed that the mutant formhad a dominant-negative effect. Furthermore, this mutant impaired the mitotic checkpoint as shown by decreased mitotic indices in HOS cells expressing mutant MAD1L1 after culture with the microtubule-disrupting agent, nocodazole, Our results suggest a pathogenic role of MAD1L1 mutations in various types of human cancer.

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Documento generato il 29/11/20 alle ore 00:41:20