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Atypical multidrug resistance in CCRF-CEM cells selected for high level methotrexate resistance: reactivity to monoclonal antibody C219 in the absence of P-glycoprotein expression.

Authors
  • 1
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
0006-291X
Publisher
Elsevier
Publication Date
Volume
165
Issue
3
Pages
1435–1441
Identifiers
PMID: 2575383
Source
Medline

Abstract

A series of CCRF-CEM sublines selected for extreme resistance to methotrexate has been shown previously to exhibit cross resistance to a number of agents belonging to the multidrug resistance phenotype (J.Natl.Cancer Inst.1989; 81, 1250-1254). The role of the mdr1 gene and its product (P-glycoprotein) in this atypical pattern of multidrug resistance has now been investigated. Southern and Northern analyses failed to demonstrate any amplification, rearrangement or over-expression of the mdr1 gene in the drug-resistant cells. Similarly, monoclonal antibodies MRK16 and JSB1 revealed no increase in the amount of P-glycoprotein present. By contrast, monoclonal antibody C219 detected a 170 kDa protein in all sublines, and in highest concentration in the most resistant cells. The results raise the possibility that a novel, C219-reactive protein may mediate resistance to both methotrexate and members of the multidrug resistance family.

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