Expression of the IAPs in multidrug resistant tumor cells

  • Authors:
    • Monica Notarbartolo
    • Melchiorre Cervello
    • Paola Poma
    • Luisa Dusonchet
    • Maria Meli
    • Natale D'Alessandro
  • View Affiliations

  • Published online on: January 1, 2004     https://doi.org/10.3892/or.11.1.133
  • Pages: 133-136
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Abstract

We have investigated the expression of the IAPs (inhibitory of apoptosis proteins) in the human HL-60 leukemia and in its multidrug resistant, P-glycoprotein (P-gp) over-expressing variant, HL-60R. HL-60R exhibits resistance to apoptosis induced from P-gp substrate drugs and also from other triggers (cisplatin, TNF-α, Fas ligation, TRAIL, IFN-γ and serum starvation) not related to the multidrug transporter. Except for c-IAP-1 mRNA, HL-60R significantly over-expressed both the mRNAs and the proteins of all the IAPs studied, i.e. c-IAP-1, c-IAP-2, XIAP, NAIP and survivin. Determination of the DNA-binding capacity of NF-κB (p50 or p65 subunits) indicated that, while HL-60 cells show constitutive activation of p50 only, HL-60R cells contain the activated forms of both p50 and p65. Since p65 is necessary to form the NF-κB heterodimers able to increase transcription, its presence in HL-60R cells might well correlate to their increased levels of IAPs and, possibly of P-gp, which, reportedly, are NF-κB target genes. These results underline the possible role that the coordinated over-expression of the different IAPs may play in tumor cell resistance to drug induced apoptosis. Inhibition of NF-κB might be a useful strategy to block their up-regulation.

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January 2004
Volume 11 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Notarbartolo M, Cervello M, Poma P, Dusonchet L, Meli M and D'Alessandro N: Expression of the IAPs in multidrug resistant tumor cells. Oncol Rep 11: 133-136, 2004.
APA
Notarbartolo, M., Cervello, M., Poma, P., Dusonchet, L., Meli, M., & D'Alessandro, N. (2004). Expression of the IAPs in multidrug resistant tumor cells. Oncology Reports, 11, 133-136. https://doi.org/10.3892/or.11.1.133
MLA
Notarbartolo, M., Cervello, M., Poma, P., Dusonchet, L., Meli, M., D'Alessandro, N."Expression of the IAPs in multidrug resistant tumor cells". Oncology Reports 11.1 (2004): 133-136.
Chicago
Notarbartolo, M., Cervello, M., Poma, P., Dusonchet, L., Meli, M., D'Alessandro, N."Expression of the IAPs in multidrug resistant tumor cells". Oncology Reports 11, no. 1 (2004): 133-136. https://doi.org/10.3892/or.11.1.133