Involvement of MDR1 function in proliferation of tumour cells.
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.
Katoh
Shin-Ya
SY
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, Japan.
Ueno
Masaya
M
Takakura
Nobuyuki
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D012004:Rectal Neoplasms / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers