Comparison of DR5 and Fas expression levels relative to the chemosensitivity of acute lymphoblastic leukemia cell lines.
The relationship between p53 gene status and the expression of DR5 and Fas was evaluated as a function of sensitivity of 11 acute lymphoblastic leukemia cell lines to adriamycin, etoposide, vincristine, methotrexate and dexamethasone. There was up to a 37-fold increase in expression of DR5 following treatment with ADR or VP-16 only in cells with wt p53. A direct correlation was observed between enhanced DR5 expression and sensitivity to ADR and VP-16. There was no induction of DR5 following treatment with VCR, MTX or DEX. There was up to a 51-fold increase in the median level of expression of Fas following treatment with ADR and VP-16, and unlike DR5 this occurred in cells with either wild-type or mutant p53. Nevertheless, a direct correlation was observed between Fas expression and drug-sensitivity. Conversely, there was only a two-fold increase in expression of Fas after exposure to VCR, MTX and DEX. These findings suggest that DR5 mediates sensitivity to ADR and VP-16 in a p53-dependent manner, whereas, Fas appears to mediate sensitivity to these two drugs independent of p53 status. DR5 and Fas do not appear to play a major role as determinants of chemosensitivity to VCR, MTX and DEX.
Lam
Viengthong
V
Department of Pharmacology, Interdepartmental Division of Oncology, University of Toronto, Ont., Canada.
Findley
Harry W
HW
Reed
John C
JC
Freedman
Melvin H
MH
Goldenberg
Gerald J
GJ
D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C505639:TNFRSF10B protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D004317:Doxorubicin