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Title: Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells

Abstract

Bone morphogenetic protein (BMP), a member of the TGF-{beta} superfamily, is involved in development, morphogenesis, cell proliferation and apoptosis. Dysregulation of BMP signaling has been suggested in tumorigenesis. In an analysis of human colon normal mucosa and tumors at different stages by immunohistochemistry, we observed that the intensity of BMP-4 staining in late-adenocarcinomas was stronger than that in normal mucosa and adenomas, while there was no difference in the staining of its receptors (BMPR-IA and BMPR-II) at all stages. The up-regulation of BMP-4 was further validated in another panel of tumor tissues by real-time RT-PCR, showing that BMP-4 mRNA levels in primary colonic carcinomas with liver metastasis were significantly higher than that in the matched normal mucosa. In order to understand the functional relevance of BMP-4 expression in colon cancer progression, BMP-4-overexpressing cell clones were generated from HCT116 cells. Overexpression of BMP-4 did not affect the HCT116 cell growth. The cells overexpressing BMP-4 became resistant to serum-starvation-induced apoptosis and exhibited enhanced migration and invasion characteristics. Overexpression of BMP-4 changed cell morphology to invasive spindle phenotype and induced the expression and activity of urokinase plasminogen activator (uPA). These results indicate that BMP-4 confers invasive phenotype during progression of colon cancer.

Authors:
 [1];  [1];  [1];  [1];  [2];  [3]
  1. Division of Surgical Research, Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, Manhasset, NY 11030 (United States)
  2. Department of Oncology, Montefiore Medical Center and Albert Einstein Cancer Center, Bronx, NY 10461 (United States)
  3. Division of Surgical Research, Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, Manhasset, NY 11030 (United States) and Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030 (United States). E-mail: wlyang@nshs.edu
Publication Date:
OSTI Identifier:
20972132
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 5; Other Information: DOI: 10.1016/j.yexcr.2006.12.020; PII: S0014-4827(07)00004-3; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADENOMAS; APOPTOSIS; CELL PROLIFERATION; LARGE INTESTINE; LIVER; METASTASES; MORPHOGENESIS; MORPHOLOGY; MUCOUS MEMBRANES; PHENOTYPE; PLASMINOGEN; POLYMERASE CHAIN REACTION; RECEPTORS; SKELETON; UROKINASE

Citation Formats

Deng Haiyun, Makizumi, Ryouji, Ravikumar, T.S., Dong Huali, Yang Wancai, and Yang, W.-L.. Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2006.12.020.
Deng Haiyun, Makizumi, Ryouji, Ravikumar, T.S., Dong Huali, Yang Wancai, & Yang, W.-L.. Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells. United States. doi:10.1016/j.yexcr.2006.12.020.
Deng Haiyun, Makizumi, Ryouji, Ravikumar, T.S., Dong Huali, Yang Wancai, and Yang, W.-L.. Sat . "Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells". United States. doi:10.1016/j.yexcr.2006.12.020.
@article{osti_20972132,
title = {Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells},
author = {Deng Haiyun and Makizumi, Ryouji and Ravikumar, T.S. and Dong Huali and Yang Wancai and Yang, W.-L.},
abstractNote = {Bone morphogenetic protein (BMP), a member of the TGF-{beta} superfamily, is involved in development, morphogenesis, cell proliferation and apoptosis. Dysregulation of BMP signaling has been suggested in tumorigenesis. In an analysis of human colon normal mucosa and tumors at different stages by immunohistochemistry, we observed that the intensity of BMP-4 staining in late-adenocarcinomas was stronger than that in normal mucosa and adenomas, while there was no difference in the staining of its receptors (BMPR-IA and BMPR-II) at all stages. The up-regulation of BMP-4 was further validated in another panel of tumor tissues by real-time RT-PCR, showing that BMP-4 mRNA levels in primary colonic carcinomas with liver metastasis were significantly higher than that in the matched normal mucosa. In order to understand the functional relevance of BMP-4 expression in colon cancer progression, BMP-4-overexpressing cell clones were generated from HCT116 cells. Overexpression of BMP-4 did not affect the HCT116 cell growth. The cells overexpressing BMP-4 became resistant to serum-starvation-induced apoptosis and exhibited enhanced migration and invasion characteristics. Overexpression of BMP-4 changed cell morphology to invasive spindle phenotype and induced the expression and activity of urokinase plasminogen activator (uPA). These results indicate that BMP-4 confers invasive phenotype during progression of colon cancer.},
doi = {10.1016/j.yexcr.2006.12.020},
journal = {Experimental Cell Research},
number = 5,
volume = 313,
place = {United States},
year = {Sat Mar 10 00:00:00 EST 2007},
month = {Sat Mar 10 00:00:00 EST 2007}
}
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