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Publication : Inhibition of epidermal growth factor receptor tyrosine kinase fails to suppress adenoma formation in ApcMin mice but induces duodenal injury.

First Author  Ritland SR Year  2000
Journal  Cancer Res Volume  60
Issue  17 Pages  4678-81
PubMed ID  10987266 Mgi Jnum  J:64399
Mgi Id  MGI:1889176 Citation  Ritland SR, et al. (2000) Inhibition of epidermal growth factor receptor tyrosine kinase fails to suppress adenoma formation in ApcMin mice but induces duodenal injury. Cancer Res 60(17):4678-81
abstractText  A highly selective, p.o. bioavailable irreversible inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, N-[4-(3-chloro4-fluorophenylamino)-quinazolin-6-yl]-ac rylamide (CFPQA), was evaluated for its ability to prevent intestinal adenoma formation in ApcMin mice. Ten-week continuous dietary exposure to CFPQA at doses sufficient to abolish intestinal EGFR tyrosine phosphorylation failed to affect intestinal tumor multiplicity or distribution but induced flat mucosal lesions in the duodenum characteristic of chronic injury. Intestinal trefoil factor, an intestinal peptide that mediates antiapoptotic effects through an EGFR-dependent mechanism, was notably absent in adenomas but was highly expressed in flat duodenal lesions. We conclude that chronic inhibition of EGFR tyrosine kinase by CFPQA does not prevent adenomas in ApcMin mice but may induce duodenal injury.
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