Stromal inactivation of BMPRII leads to colorectal epithelial overgrowth and polyp formation

Stromal–epithelial interactions play a central role in development and tumorigenesis. Bone morphogenetic protein (BMP) signaling in the intestine is involved in both of these processes. Inactivation of BMP pathway genes in the epithelium is known to cause intestinal polyposis. However, the role of t...

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Bibliographic Details
Published in:	Oncogene Vol. 27; no. 8; pp. 1063 - 1070
Main Authors:	Beppu, H, Mwizerwa, O N, Beppu, Y, Dattwyler, M P, Lauwers, G Y, Bloch, K D, Goldstein, A M
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 14-02-2008 Nature Publishing Nature Publishing Group
Subjects:	Animals Apoptosis Biological and medical sciences Bone Morphogenetic Protein Receptors, Type II - antagonists & inhibitors Bone Morphogenetic Protein Receptors, Type II - metabolism Bone morphogenetic proteins Bone Morphogenetic Proteins - metabolism Cell Biology Cell Communication - genetics Cell growth Cell physiology Cell Proliferation Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cellular signal transduction Colon Colonic Polyps - metabolism Colonic Polyps - pathology Colorectal cancer Epithelial cells Epithelium Fundamental and applied biological sciences. Psychology Gene expression Genetic aspects Genetic disorders Hamartoma - genetics Hamartoma - pathology Human Genetics Hyperplasia Hyperplasia - genetics Hyperplasia - pathology Integrases - genetics Intermediate Filament Proteins - genetics Internal Medicine Intestinal Mucosa - cytology Intestinal Mucosa - metabolism Intestinal Mucosa - pathology Intestinal polyposis Intestine Kinases Medicine Medicine & Public Health Mesenchyme Mice Mice, Transgenic Microenvironments Molecular and cellular biology Mucosa Mutation Nerve Tissue Proteins - genetics Nestin Oncology original-article Physiological aspects Polyposis Polyps Proteins Rectum - pathology Risk factors Signal transduction Stroma Stromal Cells - metabolism Stromal Cells - pathology Tumorigenesis United States hamartomatous polyps colorectal polyps stromal–epithelial interactions nestin bone morphogenetic proteins BMPRII Bone morphogenetic protein nestin hamartomatous polyps stromal- epithelial interactions Epithelium Inactivation Carcinogenesis Polyp
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Summary:	Stromal–epithelial interactions play a central role in development and tumorigenesis. Bone morphogenetic protein (BMP) signaling in the intestine is involved in both of these processes. Inactivation of BMP pathway genes in the epithelium is known to cause intestinal polyposis. However, the role of the intestinal stroma in polyp initiation is incompletely understood. We observed that conditional inactivation of the BMP type II receptor (BMPRII) in the stroma leads to epithelial hyperplasia throughout the colon with increased epithelial cell proliferation. Mutant mice developed rectal bleeding and hamartomatous polyps in the colorectum. The polyps demonstrated increased proliferation of epithelial and mesenchymal cells in the mucosa with an expansion of the myofibroblast cell population. These results demonstrate that genetic mutations altering the BMP signaling pathway in the stromal microenvironment can lead to epithelial tumors in the colon.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0950-9232 1476-5594
DOI:	10.1038/sj.onc.1210720