P-glycoprotein subcellular localization and cell morphotype in MDR1 gene-transfected human osteosarcoma cells

Research output: Contribution to journalArticlepeer-review

Abstract

Efflux of chemotherapy agents by P-glycoprotein at the plasma membrane is thought to be a major cause of cancer multidrug-resistance (MDR). However, the mechanism underlying the cellular accumulation and distribution of cytotoxic drugs is still poorly defined. We have recently found that P-glycoprotein is expressed also in the nucleus of MDR cell lines selected in doxorubicin (DXR), suggesting the possible involvement of this protein in the direct extrusion of the drug from the nucleus of resistant cells. In this study, we analyzed the subcellular localization of P-glycoprotein in a series of U-2 OS osteosarcoma cell clones transfected with MDR1 gene in order to verify whether the nucleus is a constant site for the localization and functional activity of P-glycoprotein, and in which way some aspects of cell morphology related to MDR depend on the subcellular P-glycoprotein localization rather than on the exposure to the selective drug. Our results indicate that to achieve a subcellular drug distribution prevailing in the cytoplasm but not in the nucleus, a significant increase in the expression of P-glycoprotein at the different cellular compartments, including the plasma membrane, the cytoplasm, and the nucleus, is needed, although the in vitro drug resistance appears to be mainly dependent on the expression of P-glycoprotein at the cell surface. With regard to the morphological characteristics of MDR cells involving the cell surface and the chromatin arrangement, the influence of DXR appears to be prevalent, although P-glycoprotein overexpression cannot be excluded. (C) Elsevier, Paris.

Original languageEnglish
Pages (from-to)17-28
Number of pages12
JournalBiology of the cell / under the auspices of the European Cell Biology Organization
Volume91
Issue number1
DOIs
Publication statusPublished - 1999

Keywords

  • Human osteosarcoma
  • MDR1 gene transfection
  • Multidrug-resistance (MDR)
  • P-glycoprotein localization
  • Quantitative morphology

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'P-glycoprotein subcellular localization and cell morphotype in MDR1 gene-transfected human osteosarcoma cells'. Together they form a unique fingerprint.

Cite this