International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 89 - IMPORTANCE OF EPIDERMAL GROWTH FACTOR RECEPTOR SIGNALING IN ESTABLISHMENT OF ADENOMAS AND MAINTENANCE OF CARCINOMAS DURING INTESTINAL TUMORIGENESIS

Reade Bruce Roberts
University of North Carolina Genetics Department
Threadgill Lab
UNC Dept of Genetics
11-109 Lineberger Cancer Center
Chapel Hill, NC 27599-7264
USA

Co-Authors: Min L.; Washington MK, Olsen, SJ, Coffey RJ, Threadgill DW
Institutions: Departments of Cell Biology, Pathology, Medicine, and Vanderbilt-Ingram Cancer Center, Vanderbilt University, and Veterans Affairs Medical Center

We utilized the hypomorphic Egfrwa2 allele to genetically examine the impact of impaired Egfr signaling on the ApcMin mouse model of Familial Adenomatous Polyposis (FAP). Transfer of the ApcMin allele onto a homozygous Egfrwa2 background results in up to a 97-percent reduction in intestinal polyp number relative to ApcMin mice carrying a wild-type Egfr allele. This Egfr effect may be synergistic with the actions of the Modifier-of-Min (Mom1) locus. Surprisingly, the size, expansion, and pathological progression of the polyps appear Egfr-independent. Histological examination of the ilea of younger animals revealed no differences in the numbers of nuclear b-catenin positive cells, a marker for Apc loss, or of microadenomas, the presumptive precursor lesions to gross intestinal polyps. Pharmacological inhibition with EKI-785, an Egfr tyrosine kinase inhibitor, produced similar results in the ApcMin model. These data suggest that normal Egfr activity is required for establishment of intestinal tumors in the ApcMin model between initiation and subsequent expansion of initiated tumors. The role of Egfr signaling during later stages of tumorigenesis was examined using nude mice xenografts of two human colorectal cancer (CRC) cell lines. Treatment with EKI-785 produced a dose-dependent reduction in tumor growth, suggesting that Egfr inhibitors may be useful for advanced CRC treatment.


Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url http://imgs.org
Last modified: Saturday, November 3, 2012