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

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

Research output: Contribution to journalArticle

44 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 Apc Min/+ 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 -/- , Apc Min/+ mice compared with mdr1a +/+ , Apc Min/+ 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 -/- , Apc Min/+ 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

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P-Glycoprotein
Polyps
Carcinogenesis
Enterocytes
Active Biological Transport
Large Intestine
Xenobiotics
Intestinal Mucosa
DNA Damage
Small Intestine
Intestines
Alleles
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Mochida, Y., Taguchi, K. I., Taniguchi, S., Tsuneyoshi, M., Kuwano, H., Tsuzuki, T., ... Wada, M. (2003). The role of P-glycoprotein in intestinal tumorigenesis: Disruption of mdr1a suppresses polyp formation in Apc Min/+ mice. Carcinogenesis, 24(7), 1219-1224. https://doi.org/10.1093/carcin/bgg073

The role of P-glycoprotein in intestinal tumorigenesis : Disruption of mdr1a suppresses polyp formation in Apc Min/+ mice. / Mochida, Yasushi; Taguchi, Ken Ichi; Taniguchi, Shuichi; Tsuneyoshi, Masazumi; Kuwano, Hiroyuki; Tsuzuki, Teruhisa; Kuwano, Michihiko; Wada, Morimasa.

In: Carcinogenesis, Vol. 24, No. 7, 01.07.2003, p. 1219-1224.

Research output: Contribution to journalArticle

Mochida, Y, Taguchi, KI, Taniguchi, S, Tsuneyoshi, M, Kuwano, H, Tsuzuki, T, Kuwano, M & Wada, M 2003, 'The role of P-glycoprotein in intestinal tumorigenesis: Disruption of mdr1a suppresses polyp formation in Apc Min/+ mice', Carcinogenesis, vol. 24, no. 7, pp. 1219-1224. https://doi.org/10.1093/carcin/bgg073
Mochida, Yasushi ; Taguchi, Ken Ichi ; Taniguchi, Shuichi ; Tsuneyoshi, Masazumi ; Kuwano, Hiroyuki ; Tsuzuki, Teruhisa ; Kuwano, Michihiko ; Wada, Morimasa. / The role of P-glycoprotein in intestinal tumorigenesis : Disruption of mdr1a suppresses polyp formation in Apc Min/+ mice. In: Carcinogenesis. 2003 ; Vol. 24, No. 7. pp. 1219-1224.
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