Further characterization of cyclophosphamide resistance: expression of CD95 and of bcl-2 in a CML cell line.
Drug resistance is a common cause of treatment failure in oncology. In addition to the resistance caused by over-expression of p-glycoprotein and similar molecules other mechanisms are involved in the selection or induction of drug resistant tumor cells. In this study, we characterized a CML cell line made resistant to cyclophosphamide (KBM7-B5-1803) further for the expression of apoptosis promoting and inhibiting molecules. We found that KBM7-B5-1803 has a 3 4-fold over-expression of the receptor CD95 (Fas/Apo-1) compared with the parent line. The regulation of CD95 by cytokines was comparable to other types of cells. Despite the inducibility and over-expression of CD95, CD95 failed to trigger apoptosis in both the parent and the drug resistant line. The drug resistant line has a particular pattern of the expression of bcl-2 family members: bcl-2 protein and message were expressed to a similar extent, however, compared with the parent line, the message for bclx short was decreased. P-glycoprotein was not expressed in either cell line. Taken together we show here in a leukemia cell line that the phenotype of cyclophosphamide resistance is associated with a particular pattern of apoptosis-related molecules.
Department of Hematology, Anderson Cancer Center, University of Texas, Houston 77030, USA. munker@gsf.de
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Munker
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Zhao
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S
Jiang
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Snell
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Andreeff
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BS
Andersson
D017209:Apoptosis / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D003520:Cyclophosphamide