Epidermal growth factor receptor inhibits colitis-associated cancer in mice

Philip E Dubé; Fang Yan; Shivesh Punit; Nandini Girish; Steven J McElroy; M. Kay Washington; D. Brent Polk

doi:10.1172/JCI62888

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Epidermal growth factor receptor inhibits colitis-associated cancer in mice

Journal article

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Epidermal growth factor receptor inhibits colitis-associated cancer in mice

Philip E Dubé, Fang Yan, Shivesh Punit, Nandini Girish, Steven J McElroy, M. Kay Washington and D. Brent Polk

The Journal of clinical investigation, Vol.122(8), pp.2780-2792

08/01/2012

DOI: 10.1172/JCI62888

PMCID: PMC3408743

PMID: 22772467

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Abstract

Inflammatory bowel disease (IBD) is a chronic illness caused by complex interactions between genetic and environmental factors that propagate inflammation and damage to the gastrointestinal epithelium. This state of chronic inflammation increases the risk for development of colitis-associated cancer in IBD patients. Thus, the development of targeted therapeutics that can disrupt the cycle of inflammation and epithelial injury is highly attractive. However, such biological therapies, including those targeting epidermal growth factor receptor pathways, pose a risk of increasing cancer rates. Using two mouse models of colitis-associated cancer, we found that epidermal growth factor receptor inactivation accelerated the incidence and progression of colorectal tumors. By modulating inflammation and epithelial regeneration, epidermal growth factor receptor optimized the response to chronic inflammation and limited subsequent tumorigenesis. These findings provide important insights into the pathogenesis of colitis-associated cancer and suggest that epidermal growth factor–based therapies for IBD may reduce long-term cancer risk.

Details

Title: Subtitle: Epidermal growth factor receptor inhibits colitis-associated cancer in mice
Creators: Philip E Dubé - The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, California, USA
Fang Yan - The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, California, USA
Shivesh Punit - The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, California, USA
Nandini Girish - The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, California, USA
Steven J McElroy - The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, California, USA
M. Kay Washington - The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, California, USA
D. Brent Polk - The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, California, USA
Resource Type: Journal article
Publication Details: The Journal of clinical investigation, Vol.122(8), pp.2780-2792
DOI: 10.1172/JCI62888
PMID: 22772467
PMCID: PMC3408743
NLM abbreviation: J Clin Invest
ISSN: 0021-9738
eISSN: 1558-8238
Publisher: American Society for Clinical Investigation
Language: English
Date published: 08/01/2012
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics
Record Identifier: 9984093352302771

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