P-glycoprotein gene amplification and expression in multidrug-resistant murine P388 and B16 cell lines

G. Capranico, P. De Isabella, C. Castelli, R. Supino, G. Parmiani, F. Zunino

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P-glycoprotein gene (mdr1) amplification and expression were examined in murine leukaemia P388/DX and melanoma B16VDXR cell lines, which exhibit a high level of resistance to a selecting agent, doxorubicin, and express a multidrug-resistant phenotype because they are cross-resistant to multiple cytotoxic drugs. The multidrug-resistant phenotype was obtained in different conditions of selection (in vivo and in vitro of P388/DX and B16VDXR, respectively). In both multidrug-resistant cell lines, an increased expression of P-glycoprotein gene (5 kb transcript detected in Northern blots) was observed and the level of P-glycoprotein mRNA correlated with the degree of resistance. In addition, high molecular weight mRNAs homologous to mdr1 gene sequence were consistently detected only in P388/DX cells. Overexpression was associated with a high level of gene amplification only in resistant melanoma cells, whereas it occurred in P388/DX cells with a marginal increase in gene copy number. These results, suggesting that different genetic mechanisms could be responsible for P-glycoprotein overexpression, emphasise the complexity of genetic regulation that may affect tumour cell sensitivity to cytotoxic agents.

Original languageEnglish
Pages (from-to)682-685
Number of pages4
JournalBritish Journal of Cancer
Issue number5
Publication statusPublished - 1989

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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