Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Foxf2 in Intestinal Fibro… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Foxf2 in Intestinal Fibroblasts Reduces Numbers of Lgr5(+) Stem Cells and Adenoma Formation by Inhibiting Wnt Signaling

Artikel i vetenskaplig tidskrift
Författare Ali Moussavi Nik
Azadeh Reyahi
F. Ponten
Peter Carlsson
Publicerad i Gastroenterology
Volym 144
Nummer/häfte 5
Sidor 1001-1011
ISSN 0016-5085
Publiceringsår 2013
Publicerad vid Institutionen för kemi och molekylärbiologi
Sidor 1001-1011
Språk en
Länkar dx.doi.org/10.1053/j.gastro.2013.01...
Ämnesord Colon Cancer, Tumor Stroma, Mouse Model, Tumor Suppressor, epithelial-mesenchymal interactions, transcription factor foxf2, colorectal-cancer, expression patterns, indian hedgehog, self-renewal, in-vitro, colon, differentiation, disease
Ämneskategorier Cancer och onkologi, Gastroenterologi

Sammanfattning

Background & Aims The stem cell niche at the base of the intestinal crypts, as well as stemness and high clonogenicity in colon cancer cells, depend on Wnt signaling to β-catenin. Fibroblasts modulate the Wnt pathway in normal and neoplastic epithelial cells via unclear mechanisms. We investigated how in intestinal fibroblasts the forkhead transcription factor Foxf2 controls Wnt signaling to affect numbers of stem cells and formation and growth of adenomas in mice. Methods We created mice with different copy numbers of Foxf2 by generating Foxf2−/+ mice and a transgenic strain, Tg(FOXF2). Adenoma formation was investigated in ApcMin/+ mice, stem cells were counted in mice with the Lgr5–enhanced green fluorescent protein knock-in allele, proliferation was measured by incorporation of bromodeoxyuridine, Foxf2 and Sfrp1 were localized by immunohistochemistry, and signaling pathways were analyzed by quantitative polymerase chain reaction and immunoblot assays. Results Epithelial β-catenin was stabilized in Foxf2−/+ mice, resulting in increased number and size of adenomas. Tg(FOXF2) mice, however, were partially resistant to intestinal neoplasia and developed fewer and smaller adenomas; Foxf2−/+ mice developed 24-fold more tumors than Tg(FOXF2) mice. Epithelial cells of Foxf2−/+ mice also had higher numbers of Lgr5+ stem cells and greater amounts of crypt cell proliferation and expression of Myc (a target of Wnt signaling) than Tg(FOXF2) mice. Expression of Sfrp1, which encodes an extracellular inhibitor of Wnt, in fibroblasts increased with copy number of Foxf2. Conclusions Foxf2 is a fibroblast factor that inhibits paracrine Wnt signaling and restricts the crypt stem cell niche in intestines of mice. Loss of Foxf2 promotes adenoma formation and growth.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?