This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ritland, S. R. Articles by Karnes, W. E. Search for Related Content PubMed PubMed Citation Articles by Ritland, S. R. Articles by Karnes, W. E., Jr.

Inhibition of Epidermal Growth Factor Receptor Tyrosine Kinase Fails to Suppress Adenoma Formation in Apc^Min Mice but Induces Duodenal Injury¹

Tumor Biology Program, Mayo Clinic, Scottsdale, Arizona 85259 [S. R. R., S. J. G.]; Department of Cancer Research, Pfizer Global Research and Development, Ann Arbor, Michigan 48105 [D. W. F., J. M. N., A. J. B., L. A.]; and Department of Pathology [L. J. B.] and Gastrointestinal Research Unit [W. E. K.], Mayo Clinic, Rochester, Minnesota 55905

A highly selective, p.o. bioavailable irreversible inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, N-[4-(3-chloro-4-fluoro-phenylamino)-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.

This article has been cited by other articles:

				K. J. Hare, B. Hartmann, H. Kissow, J. J. Holst, and S. S. Poulsen The Intestinotrophic Peptide, GLP-2, Counteracts Intestinal Atrophy in Mice Induced by the Epidermal Growth Factor Receptor Inhibitor, Gefitinib Clin. Cancer Res., September 1, 2007; 13(17): 5170 - 5175. [Abstract] [Full Text] [PDF]

				Q.-W. Fan, K. M. Specht, C. Zhang, D. D. Goldenberg, K. M. Shokat, and W. A. Weiss Combinatorial Efficacy Achieved Through Two-Point Blockade within a Signaling Pathway--A Chemical Genetic Approach Cancer Res., December 15, 2003; 63(24): 8930 - 8938. [Abstract] [Full Text] [PDF]

				R. B. Roberts, L. Min, M. K. Washington, S. J. Olsen, S. H. Settle, R. J. Coffey, and D. W. Threadgill Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis PNAS, January 24, 2002; (2002) 32678499. [Abstract] [Full Text] [PDF]

				R. B. Roberts, L. Min, M. K. Washington, S. J. Olsen, S. H. Settle, R. J. Coffey, and D. W. Threadgill Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis PNAS, February 5, 2002; 99(3): 1521 - 1526. [Abstract] [Full Text] [PDF]