title: Comparison of DR5 and Fas expression levels relative to the chemosensitivity of acute lymphoblastic leukemia cell lines.
abstract: 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.
authors.affiliation: Department of Pharmacology, Interdepartmental Division of Oncology, University of Toronto, Ont., Canada.
authors.forename: Viengthong
authors.initials: V
authors.lastname: Lam
authors.forename: Harry W
authors.initials: HW
authors.lastname: Findley
authors.forename: John C
authors.initials: JC
authors.lastname: Reed
authors.forename: Melvin H
authors.initials: MH
authors.lastname: Freedman
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Goldenberg
mesh_terms: 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*
chemical_list: 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