| RRC ID |
41817
|
| 著者 |
Yamada T, Mori Y, Hayashi R, Takada M, Ino Y, Naishiro Y, Kondo T, Hirohashi S.
|
| タイトル |
Suppression of intestinal polyposis in Mdr1-deficient ApcMin/+ mice.
|
| ジャーナル |
Cancer Res
|
| 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.
|
| 巻・号 |
63(5)
|
| ページ |
895-901
|
| 公開日 |
2003-3-1
|
| PMID |
12615699
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
Animals
Cell Division / drug effects
Cyclosporine / pharmacology
Cytoskeletal Proteins / biosynthesis
Cytoskeletal Proteins / genetics
Gene Transfer Techniques
Genes, APC / physiology*
Genes, MDR / genetics*
Germ-Line Mutation
Intestinal Polyps / drug therapy
Intestinal Polyps / genetics*
Intestinal Polyps / metabolism
Intestinal Polyps / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Rats
Trans-Activators / biosynthesis
Trans-Activators / genetics
Verapamil / pharmacology
beta Catenin
|
| IF |
9.727
|
| 引用数 |
77
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
IEC 6(RCB0993) |
