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Journal of Biochemistry Advance Access originally published online on January 2, 2008
Journal of Biochemistry 2008 143(4):517-524; doi:10.1093/jb/mvm242
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© 2008 The Japanese Biochemical Society.

Involvement of MDR1 Function in Proliferation of Tumour 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 correspondence should be addressed. Tel: +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 multi-drug-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 tumour cells resistant to many anti-cancer drugs. Mdr1 is well studied as a multi-drug resistance transporter, but little is known regarding its other role in tumour cells. In the present study, we investigated mdr1 function in tumour cell proliferation. We silenced the mdr1 gene in tumour cells by using an RNA interference method that employed short hairpin RNA. The result showed that knockdown of mdr1 gene suppressed tumour cell proliferation in vitro, and induced the passage of the cell cycle into the G1/G0 phase. Furthermore, in a mice xenograft tumour formation assay, mdr1 knockdown of tumour cells inhibited tumour expansion. These results suggest that Mdr1 plays a role in regulation of tumour cells proliferation.

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

Abbreviations: ABC transporter, ATP-binding cassette transporter; CyA, cyclosporine A; DXR, doxorubicin; BrdU, bromodeoxyuridine; ERK1/2, extracellular signal-regulated kinase 1/2; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; MDR, multi-drug resistance; MEFs, mouse embryonic fibroblasts; Mrp, multi-drug resistance associated protein; MTT, 3-[4,5-dimethylthiazol-2-yl]- 2,5-diphenyl-tetrazolium bromide; PI, propidium iodide; RNAi, RNA interference; Rs, reserpine; RT-PCR, reverse transcription-polymerase chain reaction; shRNA, short hairpin RNA


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