Reference SummaryRitland SR, Cancer Res 2000 Sep 1;60(17):4678-81

Title

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

Authors

Ritland SR; Gendler SJ; Burgart LJ; Fry DW; Nelson JM; Bridges AJ; Andress L; Karnes WE Jr

Journal

Cancer Res

Volume

Issue

Year

2000

Pages

4678-81

Abstract

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.

Links

J:64399 – MGI References
10987266 – National Library of Medicine/PubMed

Strain Notes

Strain	Note
C57BL/6J	Controls for Apc^Min/+ mice. Wild type mice, on C57BL/6J background.
C57BL/6J-Apc^Min/+	Mice were generated by mating breeding pairs purchased from The Jackson Laboratory.

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency
C57BL/6J-Apc^Min/+	Intestine - Large Intestine - Colon adenoma	N-[4-(3-chloro-4-fluoro-phenylamino)-quinazolin-6-yl]acrylamide (CFPQA)	Intestine - Large Intestine - Colon	observed
C57BL/6J-Apc^Min/+	Intestine - Large Intestine - Colon adenoma		Intestine - Large Intestine - Colon	observed
C57BL/6J-Apc^Min/+	Intestine - Large Intestine - Colon adenoma	piroxicam	Intestine - Large Intestine - Colon	observed
C57BL/6J-Apc^Min/+	Intestine - Small Intestine - Duodenum adenoma	piroxicam	Intestine - Small Intestine - Duodenum	observed
C57BL/6J-Apc^Min/+	Intestine - Small Intestine - Duodenum adenoma	N-[4-(3-chloro-4-fluoro-phenylamino)-quinazolin-6-yl]acrylamide (CFPQA)	Intestine - Small Intestine - Duodenum	observed
C57BL/6J-Apc^Min/+	Intestine - Small Intestine - Duodenum adenoma		Intestine - Small Intestine - Duodenum	observed
C57BL/6J-Apc^Min/+	Intestine - Small Intestine - Duodenum lesion	N-[4-(3-chloro-4-fluoro-phenylamino)-quinazolin-6-yl]acrylamide (CFPQA)	Intestine - Small Intestine - Duodenum	0 - observed
C57BL/6J	Intestine - Small Intestine - Duodenum lesion	N-[4-(3-chloro-4-fluoro-phenylamino)-quinazolin-6-yl]acrylamide (CFPQA)	Intestine - Small Intestine - Duodenum	observed
C57BL/6J-Apc^Min/+	Intestine - Small Intestine - Ileum adenoma		Intestine - Small Intestine - Ileum	observed
C57BL/6J-Apc^Min/+	Intestine - Small Intestine - Ileum adenoma	N-[4-(3-chloro-4-fluoro-phenylamino)-quinazolin-6-yl]acrylamide (CFPQA)	Intestine - Small Intestine - Ileum	observed
C57BL/6J-Apc^Min/+	Intestine - Small Intestine - Ileum adenoma	piroxicam	Intestine - Small Intestine - Ileum	observed
C57BL/6J-Apc^Min/+	Intestine - Small Intestine - Jejunum adenoma		Intestine - Small Intestine - Jejunum	observed
C57BL/6J-Apc^Min/+	Intestine - Small Intestine - Jejunum adenoma	N-[4-(3-chloro-4-fluoro-phenylamino)-quinazolin-6-yl]acrylamide (CFPQA)	Intestine - Small Intestine - Jejunum	observed
C57BL/6J-Apc^Min/+	Intestine - Small Intestine - Jejunum adenoma	piroxicam	Intestine - Small Intestine - Jejunum	observed
C57BL/6J-Apc^Min/+	Intestine adenoma	N-[4-(3-chloro-4-fluoro-phenylamino)-quinazolin-6-yl]acrylamide (CFPQA)	Intestine	observed
C57BL/6J-Apc^Min/+	Intestine adenoma		Intestine	observed
C57BL/6J-Apc^Min/+	Intestine adenoma	piroxicam	Intestine	observed