The role of P-glycoprotein in intestinal tumorigenesis: Disruption of mdr1a suppresses polyp formation in ApcMin/+ mice

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

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1219-1224
Number of pages6
JournalCarcinogenesis
Volume24
Issue number7
DOIs
Publication statusPublished - Jul 1 2003

All Science Journal Classification (ASJC) codes

  • Cancer Research

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