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Volume-sensitive chloride currents in four epithelial cell lines are not directly correlated to the expression of the MDR-1 gene.

Abstract
It has been shown recently that heterologous expression of human MDR-1 gene, which is responsible for multidrug resistance during cancer therapy, causes appearance of volume-sensitive Cl- currents, thus suggesting that the product of the MDR-1 gene (the P-glycoprotein) has a Cl- channel activity (Valverde, M. A., Diaz, M., Sepulveda, M. A., Gill, D. R., Hyde, S. C., and Higgins, C. F. (1992) Nature 355, 830-833). In the present work, we have tested four epithelial cell lines both for the expression of MDR-1 gene and for the presence of volume-sensitive Cl- currents. LoVo/H and LoVo/Dx cells derive from a human colon adenocarcinoma, the latter cell line being resistant to high concentrations of the antitumoral drug doxorubicin. 9HTEo- cells were obtained by transformation of human tracheal epithelium. The 9HTEo-/Dx cell line was established from these cells by selection in doxorubicin. As expected, higher levels of P-glycoprotein expression were detected in LoVo/Dx and 9HTEo-/Dx by means of reverse transcriptase polymerase chain reaction technique, indirect immunofluorescence, and Western immunoblot assays. In contrast with these data, the size of swelling-induced Cl- current was the same in the sensitive cell line and in its drug-resistant counterpart. Actually, the Cl- conductance of 9HTEo- and 9HTEo-/Dx was 4-fold higher than that of either LoVo/H or LoVo/Dx cells. This indicates that the amplitude of this conductance is not directly related to the expression of the MDR-1 gene.
AuthorsA Rasola, L J Galietta, D C Gruenert, G Romeo
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 269 Issue 2 Pg. 1432-6 (Jan 14 1994) ISSN: 0021-9258 [Print] United States
PMID7904600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Carrier Proteins
  • Chloride Channels
  • Chlorides
  • Membrane Glycoproteins
  • Doxorubicin
Topics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Carrier Proteins (metabolism)
  • Cell Line
  • Cell Size
  • Chloride Channels (physiology)
  • Chlorides (metabolism)
  • Doxorubicin (pharmacology)
  • Drug Resistance
  • Electric Conductivity (drug effects)
  • Epithelium (physiology)
  • Fluorescent Antibody Technique
  • Humans
  • Ion Channel Gating (drug effects)
  • Membrane Glycoproteins (metabolism)
  • Water-Electrolyte Balance

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