Alternate overexpression of two phosphoglycoprotein genes is associated with changes in multidrug resistance in a J774.2 cell line

L. Lothstein, S. I.H. Hsu, S. B. Horwitz, L. M. Greenberger

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

In multidrug-resistant murine J774.2 cells, the mdr1a and mdr1b genes encode the 120- and 125-kDa P-glycoprotein precursors, respectively (Hsu, S.I., Lothstein, L., and Horwitz, S.B. (1989) J. Biol. Chem. 264, 12053-12062). It is shown here that a J774.2 cell line selected for vinblastine resistance (J7.V3) switched from the 125- to 120-kDa precursor when cells that were maintained in 20 nM vinblastine were grown in 40 nM vinblastine for 20 months. The rate of switching was accelerated by growing cells in higher levels of vinblastine. These findings suggest that cells which express mdr1a have a selective growth advantage compared to cells which express mdr1b. Consistent with this hypothesis, the switching event that occurs in cells maintained at 40 nM vinblastine was correlated with 3.5-fold higher levels of resistance to vinblastine, taxol, and doxorubicin in the absence of any detectable increase in the amount of immunoreactive P-glycoprotein. These findings suggest that P-glycoproteins derived from mdr1a and mdr1b are functionally distinct.

Original languageEnglish (US)
Pages (from-to)16054-16058
Number of pages5
JournalJournal of Biological Chemistry
Volume264
Issue number27
StatePublished - Jan 1 1989

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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