Involvement of MDR1 function in proliferation of tumour cells

被引:24
作者
Katoh, Shin-Ya [1 ]
Ueno, Masaya [1 ]
Takakura, Nobuyuki [1 ]
机构
[1] Osaka Univ, Inst Microbial Dis, Dept Signal Transduct, Suita, Osaka 5650871, Japan
关键词
Mdr1; tumour; proliferation; RNAi; drug resistance;
D O I
10.1093/jb/mvm242
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:517 / 524
页数:8
相关论文
共 31 条
[1]   P-glycoprotein: from genomics to mechanism [J].
Ambudkar, SV ;
Kimchi-Sarfaty, C ;
Sauna, ZE ;
Gottesman, MM .
ONCOGENE, 2003, 22 (47) :7468-7485
[2]  
Borowski E, 2005, ACTA BIOCHIM POL, V52, P609
[3]   INTERNAL DUPLICATION AND HOMOLOGY WITH BACTERIAL TRANSPORT PROTEINS IN THE MDR1 (P-GLYCOPROTEIN) GENE FROM MULTIDRUG-RESISTANT HUMAN-CELLS [J].
CHEN, CJ ;
CHIN, JE ;
UEDA, K ;
CLARK, DP ;
PASTAN, I ;
GOTTESMAN, MM ;
RONINSON, IB .
CELL, 1986, 47 (03) :381-389
[4]   MODULATION OF ACTIVITY OF THE PROMOTER OF THE HUMAN MDR1 GENE BY RAS AND P53 [J].
CHIN, KV ;
UEDA, K ;
PASTAN, I ;
GOTTESMAN, MM .
SCIENCE, 1992, 255 (5043) :459-462
[5]   MULTIDRUG-RESISTANCE GENE (P-GLYCOPROTEIN) IS EXPRESSED BY ENDOTHELIAL-CELLS AT BLOOD-BRAIN BARRIER SITES [J].
CORDONCARDO, C ;
OBRIEN, JP ;
CASALS, D ;
RITTMANGRAUER, L ;
BIEDLER, JL ;
MELAMED, MR ;
BERTINO, JR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (02) :695-698
[6]   EXPRESSION OF THE MULTIDRUG RESISTANCE GENE-PRODUCT (P-GLYCOPROTEIN) IN HUMAN NORMAL AND TUMOR-TISSUES [J].
CORDONCARDO, C ;
OBRIEN, JP ;
BOCCIA, J ;
CASALS, D ;
BERTINO, JR ;
MELAMED, MR .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1990, 38 (09) :1277-1287
[7]   2 MEMBERS OF THE MOUSE MDR GENE FAMILY CONFER MULTIDRUG RESISTANCE WITH OVERLAPPING BUT DISTINCT DRUG SPECIFICITIES [J].
DEVAULT, A ;
GROS, P .
MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (04) :1652-1663
[8]  
Duan ZF, 2004, MOL CANCER THER, V3, P833
[9]   EXPRESSION OF A MULTIDRUG-RESISTANCE GENE IN HUMAN-TUMORS AND TISSUES [J].
FOJO, AT ;
UEDA, K ;
SLAMON, DJ ;
POPLACK, DG ;
GOTTESMAN, MM ;
PASTAN, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (01) :265-269
[10]   HOMOLOGY BETWEEN P-GLYCOPROTEIN AND A BACTERIAL HEMOLYSIN TRANSPORT PROTEIN SUGGESTS A MODEL FOR MULTIDRUG RESISTANCE [J].
GERLACH, JH ;
ENDICOTT, JA ;
JURANKA, PF ;
HENDERSON, G ;
SARANGI, F ;
DEUCHARS, KL ;
LING, V .
NATURE, 1986, 324 (6096) :485-489