To provide an adrenal and neuronal-specific disease model, we established AAAS-gene knockdown in H295R human adrenocortical tumor cells and SH-SY5Y human neuroblastoma cells by lentiviral short hairpin RNA transduction.
We have demonstrated that the expression of MAGE-A1, MAGE-A3, and NY-ESO-1 can be upregulated on neuroblastoma cells following exposure to pharmacologic levels of the demethylating agent 5-aza-2'-deoxycytidine (decitabine, DAC).
Putative methylation markers were selected from DAC-upregulated genes through a literature search and an upfront methylation-specific PCR on 20 primary neuroblastoma tumors, as well as through MBD- seq in combination with publicly available neuroblastoma tumor gene expression data.
Furthermore, focal copy number gains at the AATF locus in neuroblastoma, which is known to be almost exclusively p53-proficient, correlate with an adverse prognosis and reduced overall survival.
To this end, we used an inducible siRNA (small interfering RNA) expression system to silence the expression of MRP1 and MDR1 in human neuroblastoma SH-SY5Y cells.
To rule out the possibility that multidrug resistance (MDR) genes are involved in development of acquired drug resistance in murine neuroblastoma (rMNB/MDL) cells made resistant to MDL, the expression of Mdr1a, Mdr1b, Mdr2 (multidrug resistance/P-glycoprotein), and Mrp-1 (multidrug resistance associated protein) was examined in rMNB-MDL cells.
Though Pgp expression is detectable and functional in neuroblastoma cells, but its presence does not provide much information to the complex phenomenon of chemotherapy resistance in patients.
A similar strong association has been observed between the expression of P-glycoprotein and outcome of treatment in certain malignancies in children, such as neuroblastoma, rhabdomyosarcoma, and acute lymphoblastic leukemia.
Data from present study suggest that transcriptional inactivation of MDR1 gene due to increased MDR1 promoter methylation may be a contributing factor in pathogenesis and progression of neuroblastoma tumors, and may be used in designing an effective treatment therapy to neuroblastoma patients.
Decreased expression of the N-myc oncogene in neuroblastoma cell lines SH-SY5Y and BE(2)-C, following treatment with retinoic acid, was paralleled by down-regulation of MRP gene expression, contrasting with increased expression of the MDR1 gene.
Expression of N-myc, c-myc, and MDR-1 proteins in newly established neuroblastoma cell lines: a study by immunofluorescence staining and flow cytometry.
The purpose of this study was to determine the activity of pyrazoloacridine (PZA) in neuroblastomas that have acquired high-level resistance to multiple drugs (not associated with multidrug resistance-associated protein or P-glycoprotein) during therapy, including those with loss of p53 function.
Lovastatin, a nonreversible inhibitor of HMG-CoA reductase, induced extensive cytotoxicity that was restricted to drug-resistant P-glycoprotein-expressing neuroblastoma cell lines.
Study of the mechanisms underlying the reversal of multidrug resistance of human neuroblastoma multidrug-resistant cell line SK-N-SH/MDR1 by low-intensity pulsed ultrasound.
A panel of monoclonal antibodies (MAbs) to P-glycoprotein was developed by immunization of mice with multidrug-resistant human neuroepithelioma and neuroblastoma cells.
We conclude that most neuroblastoma cell lines are sensitive to YM155 in the low nM range and that resistant cells can be sensitised by ABCB1 inhibitors.