P53 protein expression in human multidrug-resistant CEM lymphoblasts.
A role for p53 in the regulation of multidrug-resistance (MDR) has been postulated as wild-type p53 suppresses and mutant p53 specifically activates the mdr1 promoter. Moreover, changes in p53 expression and/or functions could be implicated in drug resistance. As the parental lymphoblastic CCRF-CEM cell line has been described as expressing a mutated form of p53, we have examined p53 and mdm2 protein levels in the human multidrug-resistant CEM-VLB cell line variant. These drug-resistant CEM-VLB cells, which have increased expressions of mdr1 and P-glycoprotein, displayed p53 and mdm2 protein expressions similar to those observed in their sensitive CCRF-CEM counterparts. Treatment of these drug-resistant cells with non-toxic doses of the resistance-inducing drug vinblastin induced a strong increase in p53 protein and mRNA but was ineffective on mdm2 protein expression, or mdr1 mRNA expression. These data indicate that mutant p53 protein was not overexpressed in these MDR cells. This overexpression could be induced by microtubule-active drug treatment, but, as previously observed in other sensitive cell lines, mutant p53 from these MDR cells was unable to positively regulate mdm2 gene product expression.
Rafki
N
N
GIBSA, Laboratoire de Physiologie Cellulaire, UFR Pharmacie, Université de Reims, France.
Liautaud-Roger
F
F
Devy
L
L
Trentesaux
C
C
Dufer
J
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015152:Blotting, Northern; D018432:Drug Resistance, Multiple; D006801:Humans; D007150:Immunohistochemistry; D007945:Leukemia, Lymphoid / Q000188:drug therapy* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014747:Vinblastine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D014747:Vinblastine; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2