Reference SummaryYamada T, Cancer Res 2003 Mar 1;63(5):895-901

Title

 Suppression of intestinal polyposis in Mdr1-deficient ApcMin/+ mice.

Authors

 Yamada T; Mori Y; Hayashi R; Takada M; Ino Y; Naishiro Y; Kondo T; Hirohashi S

Journal

 Cancer Res

Volume

 63

Issue

 5

Year

 2003

Pages

 895-901

Abstract

 Aberrant transactivation of a certain set of target genes by the beta-catenin and T-cell factor/lymphoid enhancer factor complex has been considered crucial for the initiation of intestinal tumorigenesis. The human multidrug resistance (MDR)1 (ABCB1) gene contains multiple beta-catenin-T-cell factor4-binding elements in its promoter and is one of the immediate targets of the complex. In the current study, we have further substantiated the biological involvement of MDR1 in intestinal tumorigenesis based on the following evidence: (a) aberrant induction of the Mdr1a (Abcb1a) gene product, P-glycoprotein, associated with nuclear accumulation of the beta-catenin protein, was observed even in nascent microscopic adenomas of Min mice; (b) Mdr1-deficient Min (Apc(Min/+)Mdr1a/b(-/-)) mice developed significantly fewer intestinal polyps than did Apc(Min/+)Mdr1a/b(+/+) mice; and (c) Inhibitors of P-glycoprotein, verapamil, and cyclosporin A had a suppressive effect on the in vitro polypoid growth of IEC6 expressing stabilized (DeltaN89) beta-catenin protein. Inhibitors of P-glycoprotein may be included in a novel class of chemopreventive agents against colorectal carcinogenesis.

Links

 J:82288 – MGI References
12615699 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.Cg-Abcb1atm1Bor Abcb1btm1Bor ApcMin/+ Pla2g2aMom1-s Mice were generated by repeatedly backcrossed FVB.129P2/OlaHsd-Abcb1atm1Bor Abcb1btm1Bor females (from Taconic Farms) to C57BL/6J-ApcMin/+J males (purchased from The Jackson Laboratory) for 6 generations, and then intercrossing offspring. Mice were referred to as N6F1.
B6.Cg-ApcMin/+ Pla2g2aMom1-s Mice were generated by repeatedly backcrossed FVB.129P2/OlaHsd-Abcb1atm1Bor Abcb1btm1Bor females (from Taconic Farms) to C57BL/6J-ApcMin/+J males (purchased from The Jackson Laboratory) for 6 generations, and then intercrossing offspring Mice were referred to as N6F1.
C57BL/6J-ApcMin/+ C57BL/6J-ApcMin/+J males were purchased from The Jackson Laboratory.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6.Cg-Abcb1atm1Bor Abcb1btm1Bor ApcMin/+ Pla2g2aMom1-s Intestine - Large Intestine - Colon polyp Intestine - Large Intestine - Colon

observed
B6.Cg-ApcMin/+ Pla2g2aMom1-s Intestine - Large Intestine - Colon polyp Intestine - Large Intestine - Colon

observed
B6.Cg-Abcb1atm1Bor Abcb1btm1Bor ApcMin/+ Pla2g2aMom1-s Intestine - Small Intestine polyp Intestine - Small Intestine

observed
B6.Cg-ApcMin/+ Pla2g2aMom1-s Intestine - Small Intestine polyp Intestine - Small Intestine

observed
C57BL/6J-ApcMin/+ Intestine adenoma Intestine

observed