ArticleThe American journal of pathology2003
MYCN enhances P-gp/MDR1 gene expression in the human metastatic neuroblastoma IGR-N-91 model.
Article in The American journal of pathology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- PHLDA1 silencing in IMR-32 human neuroblastoma cells results in ABCB1 overexpression, augments chemoresistance and leads to increased growth of tumors.Scientific reports · 2025Article
- Analyzing the Blueprint: Exploring the Molecular Profile of Metastasis and Therapeutic Resistance.International journal of molecular sciences · 2025Review
- P-glycoprotein: new insights into structure, physiological function, regulation and alterations in disease.Heliyon · 2022Review
- Shc3 promotes hepatocellular carcinoma stemness and drug resistance by interacting with β-catenin to inhibit its ubiquitin degradation pathway.Cell death & disease · 2021Article
- New Evidence for P-gp-Mediated Export of Amyloid-β PEPTIDES in Molecular, Blood-Brain Barrier and Neuronal Models.International journal of molecular sciences · 2020Article
- ATR Inhibition Potentiates PARP Inhibitor Cytotoxicity in High Risk Neuroblastoma Cell Lines by Multiple Mechanisms.Cancers · 2020Article
- Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter.Scientific reports · 2017Article
- Potential Role of CD133 Expression in the Susceptibility of Human Liver Cancer Stem-Like Cells to TRAIL.Oncology research · 2016Article
- Pygo2 activates MDR1 expression and mediates chemoresistance in breast cancer via the Wnt/β-catenin pathway.Oncogene · 2016Article
- MDR1 mediated chemoresistance: BMI1 and TIP60 in action.Biochimica et biophysica acta · 2016Article
- Cisplatin-mediated c-myc overexpression and cytochrome c (cyt c) release result in the up-regulation of the death receptors DR4 and DR5 and the activation of caspase 3 and caspase 9, likely responsible for the TRAIL-sensitizing effect of cisplatin.Medical oncology (Northwood, London, England) · 2015Article
- Sensitization of chemo-resistant human chronic myeloid leukemia stem-like cells to Hsp90 inhibitor by SIRT1 inhibition.International journal of biological sciences · 2015Article
- Glycobiology of neuroblastoma: impact on tumor behavior, prognosis, and therapeutic strategies.Frontiers in oncology · 2014Review
- LIMK2 mediates resistance to chemotherapeutic drugs in neuroblastoma cells through regulation of drug-induced cell cycle arrest.PloS one · 2013Article
- Oncogene-specific formation of chemoresistant murine hepatic cancer stem cells.Hepatology (Baltimore, Md.) · 2012Article
- A comparative proteomic study identified LRPPRC and MCM7 as putative actors in imatinib mesylate cross-resistance in Lucena cell line.Proteome science · 2012Article
- The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/beta-catenin pathway.Oncogene · 2009Article
- New approaches to pharmacotherapy of tumors of the nervous system during childhood and adolescence.Pharmacology & therapeutics · 2009Review
- Fenretinide-induced caspase-8 activation and apoptosis in an established model of metastatic neuroblastoma.BMC cancer · 2009Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite intensive high-dose chemotherapy and autologous hematopoietic stem cell transplantation, disseminated neuroblastoma (NB) frequently proves to be chemosensitive but not chemocurable, and more often so in NB-presenting MYCN amplification. To assess the direct relationship between the MYCN oncogene and chemoresistance acquisition during NB metastatic dissemination, we have studied MYCN and MDR1 genes using the human IGR-N-91 ectopic xenograft metastatic model. This characterized experimental in vitro model includes human neuroblasts derived from a subcutaneous primary tumor xenograft, disseminated blood cells, myocardium, and bone marrow (BM) metastatic cells. All IGR-N-91-derived neuroblasts harbor a consistent MYCN genomic content but, unlike primary tumor xenograft, BM, and myocardium, human neuroblasts elicit a concomitant increase in MYCN and MDR1 transcripts levels, consistent with chemoresistance phenotype and active P-gp. In contrast, no variation of MRP1 transcript level was associated with the metastatic process in this model. Using an MDR1 promoter-CAT construct, we have shown that the MycN protein activates MDR1 transcription both in exogenous transient MYCN-transfected SK-N-SH cells and in endogenous BM metastatic neuroblasts with an increase in the MYCN transcript level. Band-shift experiments indicate that IGR-N-91 cells enriched with the MycN transcription factor do bind to two E-box motifs localized within the MDR1 promoter. Overall, our data indicate that MYCN overexpression increment contributes to the acquired drug resistance that occurs throughout the NB metastatic process.
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