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Journal of Biochemistry Advance Access published online on January 2, 2008
Journal of Biochemistry, doi:10.1093/jb/mvm242
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© 2008 The Japanese Biochemical Society

Involvement of MDR1 Function In Proliferation of Tumor Cells

Shin-Ya Katoh, Masaya Ueno and Nobuyuki Takakura*

Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan

*To whom requests for reprints should be addressed: Nobuyuki Takakura, Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-8316; FAX: 81-6-6879-8314; E-mail: ntakaku{at}biken.osaka-u.ac.jp

Received December 10, 2007; Accepted December 18, 2007


  Abstract

Mdr1 is a multidrug-resistance protein, a member of the adenosine triphosphate-binding cassette family of drug transporters. MDR1 is expressed in wide variety of cells and limits absorption of toxicants into the body or tissue; however, it is also expressed in many cancer cells and can render tumor cells resistant to many anti-cancer drugs. Mdr1 is well studied as a multidrug resistance transporter, but little is known regarding its other role in tumor cells. In the present study, we investigated Mdr1 function in tumor cell proliferation. We silenced the mdr1 gene in tumor cells by using an RNA interference method that employed short hairpin RNA. The result showed that knock-down of mdr1 gene suppressed tumor cell proliferation in vitro, and induced the passage of the cell cycle into the G1/G0 phase. Furthermore, in a mice xenograft tumor formation assay, mdr1 knock-down of tumor cells inhibited tumor expansion. These results suggest that Mdr1 plays a role in regulation of tumor cells proliferation.

Key Words: Mdr1, tumor, proliferation, RNAi, drug resistance


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