Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Somatic Apc mutations are selected upon their capacity to inactivate the beta-catenin downregulating activity
Autore:
Smits, R; Hofland, N; Edelmann, W; Geugien, M; Jagmohan-Changur, S; Albuquerque, C; Breukel, C; Kucherlapati, R; Kielman, MF; Fodde, R;
Indirizzi:
Leiden State Univ, Med Ctr, MGC Dept Human & Clin Genet, NL-2333 AL Leiden, Netherlands Leiden State Univ Leiden Netherlands NL-2333 AL 3 AL Leiden, Netherlands Yeshiva Univ, Albert Einstein Coll Med, Dept Cell Biol, New York, NY 10033USA Yeshiva Univ New York NY USA 10033 Dept Cell Biol, New York, NY 10033USA CIPM, Mol Biol Lab, Lisbon, Portugal CIPM Lisbon PortugalCIPM, Mol Biol Lab, Lisbon, Portugal Yeshiva Univ, Albert Einstein Coll Med, Dept Mol Genet, New York, NY 10033USA Yeshiva Univ New York NY USA 10033 Dept Mol Genet, New York, NY 10033USA
Titolo Testata:
GENES CHROMOSOMES & CANCER
fascicolo: 3, volume: 29, anno: 2000,
pagine: 229 - 239
SICI:
1045-2257(200011)29:3<229:SAMASU>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
FAMILIAL ADENOMATOUS POLYPOSIS; TUMOR-SUPPRESSOR PROTEIN; MULTIPLE INTESTINAL NEOPLASIA; COLORECTAL TUMORS; MOUSE MODEL; GENE-PRODUCT; COLI GENE; MIN MICE; CANCER; TUMORIGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Fodde, R Leiden State Univ, Med Ctr, MGC Dept Human & Clin Genet, Wassenaarseweg 72, NL-2333 AL Leiden, Netherlands Leiden State Univ Wassenaarseweg 72 Leiden Netherlands NL-2333 AL
Citazione:
R. Smits et al., "Somatic Apc mutations are selected upon their capacity to inactivate the beta-catenin downregulating activity", GENE CHROM, 29(3), 2000, pp. 229-239

Abstract

The APC gene, originally identified as the gene for familiar adenomatous polyposis (FAP), is now considered as the true "gatekeeper" of colonic epithelial proliferation. Its main tumor suppressing activity seems to reside inthe capacity to properly regulate intracellular beta-catenin signaling. Most somatic APC mutations are detected between codons 1286 and 1513, the mutation cluster region (MCR). This clustering can be explained either by the presence of mutation-prone sequences within the MCR, or by the selective advantage provided by the resulting truncated polypeptides. Here, a Msh2-deficient mouse model (Msh2(Delta 7N)) was generated and bred with Apc(1638N) and Apc(Min) that allowed the comparison of the somatic mutation spectra along the Apc gene in the different allelic combinations. Mutations identifiedin Msh2(Delta 7N/Delta 7N) tumors are predominantly dinucleotide deletionsat simple sequence repeats leading to truncated Ape polypeptides that partially retain the 20 a.a. beta-catenin downregulating motifs. In contrast, the somatic mutations identified in the wild type Apc allele of Msh2(Delta 7N/Delta 7N)/ Apc(+/638N) and Msh(2 Delta 7N/Delta 7N)/Apc(+/Min) tumors areclustered more to the 5' end, thereby completely inactivating the beta-catenin downregulating activity of APC. These results indicate that somatic Ape mutations are selected during intestinal tumorigenesis and that inactivation of the beta-catenin downregulating function of APC is likely to represent the main selective factor. (C) 2000 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 05:22:39