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OPAC HELP

Titolo:
Mutations in the APC tumour suppressor gene cause chromosomal instability
Autore:
Fodde, R; Kuipers, J; Rosenberg, C; Smits, R; Kielman, M; Gaspar, C; van Es, JH; Bruekel, C; Wiegant, J; Giles, RH; Clevers, H;
Indirizzi:
Leiden Univ, Med Ctr, Dept Human & Clin Genet, NL-2300 RA Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2300 RA NL-2300 RA Leiden, Netherlands Leiden Univ, Med Ctr, Ctr Biomed Genet, NL-2300 RA Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2300 RA NL-2300 RA Leiden, Netherlands Univ Utrecht, Med Ctr, Dept Immunol, NL-3508 GA Utrecht, Netherlands Univ Utrecht Utrecht Netherlands NL-3508 GA 3508 GA Utrecht, Netherlands Univ Utrecht, Med Ctr, Ctr Biomed Genet, NL-3508 GA Utrecht, Netherlands Univ Utrecht Utrecht Netherlands NL-3508 GA 3508 GA Utrecht, Netherlands Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RA Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2300 RA NL-2300 RA Leiden, Netherlands
Titolo Testata:
NATURE CELL BIOLOGY
fascicolo: 4, volume: 3, anno: 2001,
pagine: 433 - 438
SICI:
1465-7392(200104)3:4<433:MITATS>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYPOSIS-COLI APC; BETA-CATENIN; PROTEIN EB1; MICROTUBULE CYTOSKELETON; GENOMIC INSTABILITY; COLORECTAL CANCERS; BINDING PROTEIN; RAS ONCOGENE; HOMOLOG; YEAST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Fodde, R Leiden Univ, Med Ctr, Dept Human & Clin Genet, POB 9503, NL-2300 RA Leiden, Netherlands Leiden Univ POB 9503 Leiden Netherlands NL-2300 RA , Netherlands
Citazione:
R. Fodde et al., "Mutations in the APC tumour suppressor gene cause chromosomal instability", NAT CELL BI, 3(4), 2001, pp. 433-438

Abstract

Two forms of genetic instability have been described in colorectal cancer(1): microsatellite instability and chromosomal instability. Microsatellite instability results from mutations in mismatch repair genes; chromosomal instability is the hallmark of many colorectal cancers, although it is not completely understood at the molecular level. As truncations of the Adenomatous Polyposis Coli (APC) gene are found in most colorectal tumours, we thought that mutations in APC might be responsible for chromosomal instability. To test this hypothesis, we examined mouse embryonic stem (ES) cells homozygous for Min (multiple intestinal neoplasia) or Apc1638T alleles, Here we show that Ape mutant ES cells display extensive chromosome and spindle aberrations, providing genetic evidence for a role of APC in chromosome segregation. Consistent with this, APC accumulates at the kinetochore during mitosis, Ape mutant cells form mitotic spindles with an abundance of microtubulesthat inefficiently connect with kinetochores. This phenotype is recapitulated by the induced expression of a 253-amino-acid carboxy-terminal fragmentof APC in microsatellite unstable colorectal cancer cells, We conclude that loss of APC sequences that lie C-terminal to the beta -catenin regulatorydomain contributes to chromosomal instability in colorectal cancer.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/10/20 alle ore 01:59:01