Journal article
Juvenile polyps have gastric differentiation with MUC5AC expression and downregulation of CDX2 and SMAD4
Histochemistry and cell biology, Vol.131(6), pp.765-772
06/2009
DOI: 10.1007/s00418-009-0579-z
PMID: 19266212
Abstract
CDX2 is a homeobox transcription factor that works as a master gene in intestinal differentiation, both in the colon and in aberrant locations such as intestinal metaplasia (IM) of the stomach. Transgenic mice with Cdx2 expression in the stomach develop IM and Cdx2+/− mice develop hamartomatous polyps in the colon presenting gastric differentiation. We previously observed regulation of CDX2 by the BMP/SMAD pathway in the gastric context. Here, we hypothesized that juvenile polyps, which are hamartomatous polyps caused by mutations in members of the BMP/SMAD pathway, might recapitulate the gastric differentiation observed in Cdx2+/− mice due to SMAD4 and CDX2 downregulation. We characterized SMAD4 and CDX2 expression in a series of 18 solitary juvenile polyps and 2 polyps from juvenile polyposis (JP) patients, one with a germline SMAD4 mutation and one with a germline BMPRIA mutation, as well as the expression of an intestinal differentiation marker, MUC2 (by immunohistochemistry and in situ hybridization), and gastric differentiation markers, MUC5AC and MUC6 (by immunohistochemistry). We observed that juvenile polyps have a heterogeneous expression of CDX2, MUC2 and SMAD4, with negative areas, and 15 of the 18 solitary polyps and the JP case with SMAD4 mutation exhibit de novo expression of MUC5AC but not MUC6. In conclusion, juvenile polyps have gastric transdifferentiation associated with downregulation of CDX2 and SMAD4, lending support to the role of the BMP/SMAD pathway in CDX2 regulation.
Details
- Title: Subtitle
- Juvenile polyps have gastric differentiation with MUC5AC expression and downregulation of CDX2 and SMAD4
- Creators
- Rita Barros - IPATIMUP, Instituto de Patologia e Imunologia Molecular da Universidade do Porto Rua Dr. Roberto Frias si/na 4200 Porto PortugalNuno Mendes - IPATIMUP, Instituto de Patologia e Imunologia Molecular da Universidade do Porto Rua Dr. Roberto Frias si/na 4200 Porto PortugalJames Howe - Department of Surgery University of Iowa College of Medicine Iowa City USACelso Reis - Faculty of Medicine University of Porto Porto PortugalCarme de Bolos - IMIM Barcelona SpainFátima Carneiro - Department of Pathology Hospital S. João Porto PortugalLeonor David - Faculty of Medicine University of Porto Porto PortugalRaquel Almeida - Faculty of Medicine University of Porto Porto Portugal
- Resource Type
- Journal article
- Publication Details
- Histochemistry and cell biology, Vol.131(6), pp.765-772
- Publisher
- Springer-Verlag; Berlin/Heidelberg
- DOI
- 10.1007/s00418-009-0579-z
- PMID
- 19266212
- ISSN
- 0948-6143
- eISSN
- 1432-119X
- Language
- English
- Date published
- 06/2009
- Academic Unit
- Surgery
- Record Identifier
- 9984051517302771
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