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Titolo:
Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway
Autore:
Wielenga, VJM; Smits, R; Korinek, V; Smit, L; Kielman, M; Fodde, R; Clevers, H; Pals, ST;
Indirizzi:
UnivsAmsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherland Univ Amsterdam Amsterdam Netherlands NL-1105 AZ AZ Amsterdam, Netherland Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands Leiden Univ Leiden Netherlands r, Dept Human Genet, Leiden, Netherlands Univ Utrecht Hosp, Dept Immunol, Utrecht, Netherlands Univ Utrecht Hosp Utrecht Netherlands ept Immunol, Utrecht, Netherlands
Titolo Testata:
AMERICAN JOURNAL OF PATHOLOGY
fascicolo: 2, volume: 154, anno: 1999,
pagine: 515 - 523
SICI:
0002-9440(199902)154:2<515:EOCIAA>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEPATOCYTE GROWTH-FACTOR; HOMING RECEPTOR CD44; METASTASIS-ASSOCIATED VARIANT; NON-HODGKINS-LYMPHOMA; BETA-CATENIN; COLORECTAL-CANCER; SCATTER FACTOR; ADENOMATOUS POLYPS; INTESTINAL TUMORS; MET PROTOONCOGENE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
66
Recensione:
Indirizzi per estratti:
Indirizzo: Pals, ST Univrdam,erdam, Acad Med Ctr, Dept Pathol, Meibergdreef 9, NL-1105 AZ Amste Univ Amsterdam Meibergdreef 9 Amsterdam Netherlands NL-1105 AZ e
Citazione:
V.J.M. Wielenga et al., "Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway", AM J PATH, 154(2), 1999, pp. 515-523

Abstract

Overexpression of cell surface glycoproteins of the CD44 family is an early event in the colorectal adenoma-carcinoma sequence. This suggests a Link with disruption of APC tumor suppressor protein-mediated regulation of beta-catenin/Tcf-4 signaling, which is crucial in initiating tumorigenesis. To explore this hypothesis, we analyzed CD44 expression in the intestinal mucosa of mice and humans with genetic defects in either APC or Tcf-4, leading to constitutive activation or blockade of the beta-catenin/Tcf-4 pathway, respectively. We show that CD44 expression in the non-neoplastic intestinal mucosa of Apc mutant mice is confined to the crypt epithelium but that CD44is strongly overexpressed in adenomas as well as in invasive carcinomas. This overexpression includes the standard part of the CD44 (CD44s) as well as variant exons (CD44v). Interestingly, deregulated CD44 expression is already present in aberrant crypt foci with dysplasia (ACFs), the earliest detectable lesions of colorectal neoplasia. Like ACFs of Apc-mutant mice, ACFs of familial adenomatous polyposis (FAP) patients also overexpress CD44, In sharp contrast, Tcf-4 mutant mice show a complete absence of CD44 in the epithelium of the small intestine. This loss of CD44 concurs with loss of stem cell characteristics, shared with adenoma cells. Our results indicate that CD44 expression is part of a genetic program controlled by the beta-catenin/Tcf-4 signaling pathway and suggest a role for CD44 in the generation and turnover of epithelial cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 13:57:40