title: Nuclear translocation of MRP1 contributes to multidrug resistance of mucoepidermoid carcinoma.
abstract: Multidrug resistance-related protein 1 (MRP1 or ABCC1), a membrane-bound energy-dependent efflux transporter, is overexpressed in several kinds of multidrug-resistant cell lines and related to multidrug-resistance (MDR) of various cancers. In this study, we investigated whether MRP1 was involved in the chemoresistance of mucoepidermoid carcinoma (MEC). We demonstrated that down-regulation of MRP1 in MC3/5FU, a drug-resistant MEC cell line, by RNA interference increased the drug sensitivity of the cells to 5-fluorouracil, doxorubicin, pharmorubicin, bleomycin-A5, cis-platinum and taxol. However, no significant quantitative difference of MRP1 mRNA and protein expression was found between MC3/5FU cells and its parental cell line (MC3) as determined by RT-PCR and Western blot. Interestingly, MRP1 was translocated from the cytoplasmic membrane of the MC3 cells to the nuclei of MC3/5FU cells as revealed by indirect immunofluorescence staining. Furthermore, MRP1 down-regulation mainly decreased the nuclear expression of MRP1 rather than the cytoplasmic membrane expression. Our results suggested that MRP1 was involved in the chemoresistance of MEC and MRP1 may confer drug-resistance by a mechanism associated with its nuclear translocation.
authors: Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, 145 Chang Le Xi Road, Xi'an 710032, China.
authors: Bo-Lei
authors: BL
authors: Cai
authors: Xiao-Fang
authors: XF
authors: Xu
authors: Shan-Min
authors: SM
authors: Fu
authors: Liang-Liang
authors: LL
authors: Shen
authors: Jing
authors: J
authors: Zhang
authors: Su-Min
authors: SM
authors: Guan
authors: Jun-Zheng
authors: JZ
authors: Wu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015251:Epirubicin / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D001761:Bleomycin; D015251:Epirubicin; C025703:bleomycetin; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil