Journal Article

The role of P-glycoprotein in intestinal tumorigenesis: disruption of <i>mdr1a</i> suppresses polyp formation in <i>Apc</i><sup>Min/+</sup> mice

Yasushi Mochida, Ken-ichi Taguchi, Shuichi Taniguchi, Masazumi Tsuneyoshi, Hiroyuki Kuwano, Teruhisa Tsuzuki, Michihiko Kuwano and Morimasa Wada

in Carcinogenesis

Volume 24, issue 7, pages 1219-1224
Published in print July 2003 | ISSN: 0143-3334
Published online July 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg073
The role of P-glycoprotein in intestinal tumorigenesis: disruption of mdr1a suppresses polyp formation in ApcMin/+ mice

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P-glycoprotein (P-gp) mediates the active transport of various substrates including xenobiotics, and it thus has a protective function in various cell types and tissues/organs including the intestinal epithelium. However, whether or not P-gp plays a positive role in the intestinal tumorigenesis is unclear. We have introduced disrupted alleles of the murine P-gp gene, mdr1a, into ApcMin/+ mice to evaluate whether P-gp plays any role in intestinal carcinogenesis. Spontaneously occurring DNA damage was significantly increased in both the small and large intestine of mdr1a−/−, ApcMin/+ mice compared with mdr1a+/+, ApcMin/+ mice. Furthermore, we observed active proliferation and rapid migration/disappearance of enterocytes in the intestine of the compound mice deficient in mdr1a. Finally, we found that the number of polyps and cancers was markedly decreased in mdr1a−/−, ApcMin/+ mice (P = 0.0016). P-gp thus appears to play a positive role during intestinal tumorigenesis.

Keywords: ABC, ATP-binding cassette; APC, adenomatous polyposis coli; BrdU, 5′-bromo-2′-deoxyuridine; 8-oxo-dG, 8-oxo-7,8-dihydro-2′-deoxyguanosine; P-gp, P-glycoprotein

Journal Article.  4099 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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