Inhibition of epidermal growth factor receptor tyrosine kinase fails to suppress adenoma formation in Apc(Min) mice but induces duodenal injury

S. R. Ritland, S. J. Gendler, L. J. Burgart, D. W. Fry, J. M. Nelson, A. J. Bridges, L. Andress, Jr Karnes

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

A highly selective, p.o. bioavailable irreversible inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, N-[4-(3-chloro-4-fluorophenylamino)-quinazolin-6-yl]-acrylamide (CFPQA), was evaluated for its ability to prevent intestinal adenoma formation in Apc(Min) 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 Apc(Min) mice but may induce duodenal injury.

Original languageEnglish (US)
Pages (from-to)4678-4681
Number of pages4
JournalCancer research
Volume60
Issue number17
StatePublished - Sep 1 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ritland, S. R., Gendler, S. J., Burgart, L. J., Fry, D. W., Nelson, J. M., Bridges, A. J., Andress, L., & Karnes, J. (2000). Inhibition of epidermal growth factor receptor tyrosine kinase fails to suppress adenoma formation in Apc(Min) mice but induces duodenal injury. Cancer research, 60(17), 4678-4681.