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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.