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 |
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Strain Notes
|
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 |