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Netrin-1 controls colorectal tumorigenesis by regulating apoptosis.
Mazelin, Laetitia; Bernet, Agnès; Bonod-Bidaud, Christelle; Pays, Laurent; Arnaud, Ségolène; Gespach, Christian; Bredesen, Dale E; Scoazec, Jean-Yves; Mehlen, Patrick.
Afiliação
  • Mazelin L; Apoptosis/Differentiation Laboratory-Equipe labellisée La Ligue-Molecular and Cellular Genetic Center, CNRS UMR 5534, University of Lyon, 69622 Villeurbanne, France.
Nature ; 431(7004): 80-4, 2004 Sep 02.
Article em En | MEDLINE | ID: mdl-15343335
ABSTRACT
The expression of the protein DCC (deleted in colorectal cancer) is lost or markedly reduced in numerous cancers and in the majority of colorectal cancers due to loss of heterozygosity in chromosome 18q, and has therefore been proposed to be a tumour suppressor. However, the rarity of mutations found in DCC, the lack of cancer predisposition of DCC mutant mice, and the presence of other tumour suppressor genes in 18q have raised doubts about the function of DCC as a tumour suppressor. Unlike classical tumour suppressors, DCC has been shown to induce apoptosis conditionally by functioning as a dependence receptor, DCC induces apoptosis unless DCC is engaged by its ligand, netrin-1 (ref. 3). Here we show that inhibition of cell death by enforced expression of netrin-1 in mouse gastrointestinal tract leads to the spontaneous formation of hyperplastic and neoplastic lesions. Moreover, in the adenomatous polyposis coli mutant background associated with adenoma formation, enforced expression of netrin-1 engenders aggressive adenocarcinomatous malignancies. These data demonstrate that netrin-1 can promote intestinal tumour development, probably by regulating cell survival. Thus, a netrin-1 receptor or receptors function as conditional tumour suppressors.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Transformação Celular Neoplásica / Apoptose / Fatores de Crescimento Neural Limite: Animals Idioma: En Ano de publicação: 2004 Tipo de documento: Article
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Transformação Celular Neoplásica / Apoptose / Fatores de Crescimento Neural Limite: Animals Idioma: En Ano de publicação: 2004 Tipo de documento: Article