Inheritance of chromosome 7 is associated with a drug-resistant phenotype in somatic cell hybrids

M. De Silva, P. Kantharidis, D. M. Wall, L. Campbell, V. Vrazas, G. Nadalin, S. J. Kaczmarczyk, X. F. Hu, J. D. Parkin, J. R. Zalcberg

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8 Citations (Scopus)

Abstract

A major form of drug resistance in tumour cells known as classical multidrug resistance (MDR) is associated with the overexpression of the mdr1 gene product, the membrane protein P-glycoprotein (P-gp), which acts as an energy-dependent drug efflux pump. In this study the inheritance of P-gp expression was examined using hybrids formed after somatic cell fusion between a drug-sensitive human T-cell leukaemia cell line, CEM/CCRF, and a drug-resistant derivative, CEM/A7, which is characterised by a clonal chromosomal duplication dup(7)(q11.23q31.2). Fourteen hybrids, chosen at random, were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) and by binding studies involving the monoclonal antibody MRK16, which recognises an external P-gp epitope. Only two hybrids were positive for both MRK16 antibody labelling and mdr1 mRNA. Partial karyotypic analysis of all hybrids revealed that only the MRK16-positive hybrids contained the duplication in chromosome 7 seen in the CEM/A7 parental MDR line. Therefore, P-gp overexpression in the MRK16-positive hybrids may be linked to the inheritance of chromosome 7 from CEM/A7 and possibly associated with the chromosome 7 abnormality.

Original languageEnglish
Pages (from-to)169-174
Number of pages6
JournalBritish Journal of Cancer
Volume73
Issue number2
Publication statusPublished - 1996
Externally publishedYes

Keywords

  • Chromosome 7
  • Drug resistance
  • P-glycoprotein
  • Somatic cell fusion

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