Format

Send to

Choose Destination
Int J Oncol. 2005 Oct;27(4):1029-37.

Increased malignant behavior in neuroblastoma cells with acquired multi-drug resistance does not depend on P-gp expression.

Author information

1
Interdisziplinäres Laboratorium für Tumor und Virus Forschung, Institut für Medizinische Virologie, Clinics of J-W. Goethe University, Frankfurt am Main, Germany.

Abstract

Acquisition of P-gp-mediated multidrug-resistance does not always correlate with observed malignant behavior of NB. To characterize alterations accompanying development of multidrug-resistance in NB we established two neuroblastoma cell sublines resistant to vincristine (UKF-NB-3rVCR10) and doxorubicin (UKF-NB-3rDOX20). UKF-NB-3rVCR10 and UKF-NB-3rDOX20 overexpressed functional P-gp and developed an increased malignant phenotype: presented constitutive phosphorylation of AKT, resistance to gamma-irradiation, and had increased survival in serum-free medium. Inhibition of P-gp restored chemosensitivity but did not affect increased survival in serum-free medium and sensitivity to gamma-irradiation. Inhibition of AKT had no influence on chemoresistance but restored sensitivity to serum starvation. Both resistant cell lines acquired additional chromosomal changes. UKF-NB-3rVCR10 cells acquired a missense P53 mutation in exon 5, an increased MYCN amplification, an enhanced adhesion to endothelium, a decreased NCAM expression, a distinctly higher clonogenicity, and an increased in vivo tumorigenicity. We conclude that acquisition of increased malignant behavior in neuroblastoma occurs concomitantly with multidrug-resistance and is P-gp-independent.

PMID:
16142320
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Spandidos Publications
Loading ...
Support Center