Distinct P-glycoprotein precursors are overproduced in independently isolated drug-resistant cell lines

L. M. Greenberger, Leonard Lothstein, S. S. Williams, S. B. Horwitz

Research output: Contribution to journalArticle

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Abstract

A family of P-glycoproteins are overproduced in multidrug-resistant cells derived from the murine macrophage-like J774.2. To determine whether individual family members are overproduced in response to different drugs, the P-glycoprotein precursors in several independently isolated cell lines, which were selected for resistance to vinblastine or taxol, were compared. Individual cell lines selected with vinblastine overproduced P-glycoprotein precursors of either 120 or 125 kDa. Taxol-selected cell lines overproduced either the 125-kDa precursor or both precursors simultaneously. Two similar but distinct peptide maps for the mature P-glycoproteins were observed. These maps corresponded to each precursor regardless of the drug used for selection. One vinblastine-resistant cell line switched from the 125- to the 120-kDa precursor when grown in increasing concentrations of drug. This change coincided with the overexpression of a distinct subset of mRNA species that code for P-glycoprotein. It is concluded that precursor expression is not drug-specific. These data suggest that individual overproduced P-glycoprotein family members are translated as distinct polypeptides. The results may help to explain the diversity in the multidrug-resistant phenotype.

Original languageEnglish (US)
Pages (from-to)3762-3766
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number11
DOIs
StatePublished - Jan 1 1988

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P-Glycoprotein
Vinblastine
P-Glycoproteins
Cell Line
Paclitaxel
Pharmaceutical Preparations
Peptides
Prodrugs
Macrophages
Phenotype
Messenger RNA

All Science Journal Classification (ASJC) codes

  • General

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Distinct P-glycoprotein precursors are overproduced in independently isolated drug-resistant cell lines. / Greenberger, L. M.; Lothstein, Leonard; Williams, S. S.; Horwitz, S. B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 85, No. 11, 01.01.1988, p. 3762-3766.

Research output: Contribution to journalArticle

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AB - A family of P-glycoproteins are overproduced in multidrug-resistant cells derived from the murine macrophage-like J774.2. To determine whether individual family members are overproduced in response to different drugs, the P-glycoprotein precursors in several independently isolated cell lines, which were selected for resistance to vinblastine or taxol, were compared. Individual cell lines selected with vinblastine overproduced P-glycoprotein precursors of either 120 or 125 kDa. Taxol-selected cell lines overproduced either the 125-kDa precursor or both precursors simultaneously. Two similar but distinct peptide maps for the mature P-glycoproteins were observed. These maps corresponded to each precursor regardless of the drug used for selection. One vinblastine-resistant cell line switched from the 125- to the 120-kDa precursor when grown in increasing concentrations of drug. This change coincided with the overexpression of a distinct subset of mRNA species that code for P-glycoprotein. It is concluded that precursor expression is not drug-specific. These data suggest that individual overproduced P-glycoprotein family members are translated as distinct polypeptides. The results may help to explain the diversity in the multidrug-resistant phenotype.

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