Molecular/cytogenetic alterations accompanying the development of multidrug resistance in the J774.2 murine cell line

M. L. Slovak, L. Lothstein, S. B. Horwitz, J. M. Trent

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Mouse macrophage-like J774.2 cells were selected for resistance to colchicine and examined by molecular/cytogenetic analysis to determine whether the acquisition of the multidrug resistant (mdr) phenotype was associated with specific chromosomal rearrangements. Cytogenetic studies of the J774.2 parental and two colchicine-resistant (CLC(R)) sublines-J7.Cl-30 (770-fold CLC(R)) and J7.Cl-100 (2500-fold CLC(R))-demonstrated specific numeric and structural karyotypic alterations accompanying the emergence of mdr. The parenteral cells demonstrated a modal chromosome number of 63, while the modal number of the J7.Cl-30 subline was 53. The most striking difference between the parental and J7.Cl-30 subline was the presence of an average of 60 double minutes (DMs) per cell in the CLC(R) cells. The 2500-fold resistant J7.Cl-100 subline displayed a modal number of 50, which included structural rearrangements involving chromosomes 2 and 7 and concomitant replacement of DMs by a homogeneously staining region (HSR).Southern blotting analysis demonstrated a ~35-fold amplification of P-glycoprotein homologous sequences in the J7.Cl-100 subline and ~70-fold amplification in the J7.Cl-100 subline. Chromosomal in situ hybridization localized the amplified P-glycoprotein sequences to DMs (J7.Cl-30) and the HSR (J7.Cl-100) in these CLC(R) sublines. Our results suggest that CLC(R) in J774.2 cells results from overexpression of P-glycoprotein via gene amplification which was accompanied by chromosomal evolution from DMs to an HSR.

Original languageEnglish (US)
Pages (from-to)453-458
Number of pages6
JournalLeukemia
Volume2
Issue number7
StatePublished - 1988
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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