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

• 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
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210720

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.