ArticlePharmaceutical research2009
Pharmacogenomics approach reveals MRP1 (ABCC1)-mediated resistance to geldanamycins.
Article in Pharmaceutical research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Near Infrared Photoimmunotherapy for Lung Cancer: Recent Development and Perspective.ImmunoTargets and therapy · 2026Review
- How Cryo-EM Has Expanded Our Understanding of Membrane Transporters.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- A redox-responsive self-assembling COA-4-arm PEG prodrug nanosystem for dual drug delivery suppresses cancer metastasis and drug resistance by downregulating hsp90 expression.Acta pharmaceutica Sinica. B · 2023Article
- Role of multidrug resistance-associated proteins in cancer therapeutics: past, present, and future perspectives.Environmental science and pollution research international · 2021Review
- Cytokine-Induced Killer Cells Modulates Resistance to Cisplatin in the A549/DDP Cell Line.Journal of Cancer · 2017Article
- Calpain Genetic Disruption and HSP90 Inhibition Combine To Attenuate Mammary Tumorigenesis.Molecular and cellular biology · 2016Article
- Development of a cyclin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance.British journal of cancer · 2013Article
- Transport processes of radiopharmaceuticals and -modulators.Radiation oncology (London, England) · 2011Review
- Pharmacogenomic discovery using cell-based models.Pharmacological reviews · 2009Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeGeldanamycin and its analogues belong to a new class of anticancer agents that inhibit the molecular chaperone heat shock protein 90. We hypothesized that membrane transporters expressed on tumor cells may contribute at least in part to cellular sensitivity to these agents. The purpose of this study is to identify novel transporters as determinant for sensitivity and resistance to geldanamycins.
methodsTo facilitate a systematic study of chemosensitivity across multiple geldanamycin analogues, we correlated mRNA expression profiles of majority of transporters with anticancer drug activities in 60 human tumor cell lines (NCI-60). We subsequently validated the gene-drug correlations using cytotoxicity and transport assays.
resultsThe GA analogues displayed negative correlations with mRNA expression levels of the multidrug resistance protein 1 (MRP1, ABCC1). Suppressing MRP1 efflux using the inhibitor MK-571 and small interfering RNA in cell lines with intrinsic and acquired MRP1 overexpression (A549 and HL-60/ADR) and in cell lines stably transduced with MRP1 (MCF7/MRP1) increased intracellular drug accumulation and increased tumor cell sensitivity to geldanamycin analogues.
conclusionsThese results suggest that elevated expression of MRP1, like the alternative efflux transporter MDR1 (ABCB1, P-glycoprotein), can significantly influence tumor cell sensitivity to geldanamycins as a potential chemoresistance factor.
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