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

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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.

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APA

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 ApcMin/+ mice. Carcinogenesis, 24(7), 1219–1224. https://doi.org/10.1093/carcin/bgg073

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