| Induction of cellular resistance to nucleoside reverse transcriptase inhibitors by the wild-type breast cancer resistance protein. | |
| | |
MedLine Citation:
|
PMID: 15345326 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Breast cancer resistance protein (BCRP/ABCG2) is a novel member of ATP-binding cassette transporters, which induce multidrug resistance in cancer cells. We previously reported that a high level of BCRP expression in CD4(+) T cells conferred cellular resistance to nucleoside reverse transcriptase inhibitors (NRTIs) of human immunodeficiency virus type 1 (HIV-1). However, this BCRP was found to have a mutation of Arg to Met at position 482 (BCRP(R482M)). The present study demonstrated that the wild-type BCRP (BCRP(WT)) also conferred cellular resistance to NRTIs. MT-4 cells (a CD4(+) T-cell line) highly expressing BCRP(WT) (MT-4/BCRP) were generated and the expression of BCRP(WT) was confirmed by genotypic and phenotypic analyses. Compared to the parental MT-4 cells, MT-4/BCRP cells displayed resistance to zidovudine (AZT) in terms of antiviral activity as well as drug cytotoxicity. In addition, other NRTIs were also less inhibitory to HIV-1 replication in MT-4/BCRP cells than in MT-4 cells. Significant reduction of intracellular AZT accumulation was observed in MT-4/BCRP cells. An analysis for intracellular metabolism of AZT suggested that the resistance was attributed to the increased efflux of AZT and its metabolites in MT-4/BCRP cells. Furthermore, the BCRP-specific inhibitor fumitremorgin C completely restored the reduction of AZT in MT-4/BCRP cells. These results indicate that, like BCRP(R482M), BCRP(WT) also plays an important role in cellular resistance to NRTIs. |
| | |
Authors:
|
Xin Wang; Takao Nitanda; Minyi Shi; Mika Okamoto; Tatsuhiko Furukawa; Yoshikazu Sugimoto; Shin-ichi Akiyama; Masanori Baba |
Related Documents
:
|
1140866 - The effect of non-ionic detergent tween 80 on colcemid-resistant transformed mouse cell... 6209556 - Dna methylation in 5-aza-2'-deoxycytidine-resistant variants of c3h 10t1/2 c18 cells. 20707406 - Sensitization of non-small cell lung cancer cells to cisplatin by naturally occurring i... 20446926 - (-)-epigallocatechin-3-gallate down-regulates egfr, mmp-2, mmp-9 and emmprin and inhibi... 21999456 - Atp-dependent chromatin remodeling in t cells. 1380886 - Expression of human prostatic acid phosphatase activity and the growth of prostate carc... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Biochemical pharmacology Volume: 68 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2004 Oct |
Date Detail:
|
Created Date: 2004-09-03 Completed Date: 2004-11-03 Revised Date: 2004-11-17 |
Medline Journal Info:
|
Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
|
Languages: eng Pagination: 1363-70 Citation Subset: IM |
Affiliation:
|
Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
ATP-Binding Cassette Transporters
/
antagonists & inhibitors,
physiology* Anti-HIV Agents / pharmacokinetics, pharmacology* Antineoplastic Agents, Phytogenic / pharmacology* CD4-Positive T-Lymphocytes / drug effects*, metabolism Cell Survival / drug effects Cells, Cultured Doxorubicin / pharmacology Drug Resistance, Multiple / physiology* Drug Resistance, Neoplasm HIV-1 / drug effects Humans Indoles / pharmacology Neoplasm Proteins / antagonists & inhibitors, physiology* Reverse Transcriptase Inhibitors / pharmacology* Zidovudine / pharmacokinetics, pharmacology |
| Chemical | |
Reg. No./Substance:
|
0/ABCG2 protein, human; 0/ATP-Binding Cassette Transporters; 0/Anti-HIV Agents; 0/Antineoplastic Agents, Phytogenic; 0/Indoles; 0/Neoplasm Proteins; 0/Reverse Transcriptase Inhibitors; 23214-92-8/Doxorubicin; 30516-87-1/Zidovudine; 55387-45-6/tryptoquivaline |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Evidence for multiple glucuronide transporters in rat liver microsomes.
Next Document: Determination of interleukin-4-responsive region in the human cytochrome P450 2E1 gene promoter.