RRC ID 38923
Author Kondo S, Kondo Y, Hara H, Kaakaji R, Peterson JW, Morimura T, Takeuchi J, Barnett GH.
Title mdm2 gene mediates the expression of mdr1 gene and P-glycoprotein in a human glioblastoma cell line.
Journal Br J Cancer
Abstract The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumours. The mechanism by which mdr1 gene and P-gp are overexpressed in human tumours, however, is not yet clear. In this report, we show that the mdm2 (murine double minute 2) gene induced the expression of the mdr1 gene and P-gp in human glioblastoma U87-MG cells, which did not express the MDM2 protein or P-gp. The mdm2 gene, in addition, conferred the resistance of U87-MG cells to the apoptotic cell death induced by etoposide (VP-16) or doxorubicin. Furthermore, treatment with mdm2 antisense oligonucleotides inhibited the expression of P-gp in MDM2-expressing U87-MG cells. These findings suggest that the mdm2 gene may play an important role in the development of MDR phenotype in human tumours.
Volume 74(8)
Pages 1263-8
Published 1996-10-1
DOI 10.1038/bjc.1996.527
PMID 8883415
PMC PMC2075914
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis* ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics* Antibiotics, Antineoplastic / pharmacology Antineoplastic Agents, Phytogenic / pharmacology Apoptosis / physiology Doxorubicin / pharmacology Drug Resistance, Multiple / genetics* Etoposide / pharmacology Gene Expression Regulation, Neoplastic Glioblastoma / genetics* Glioblastoma / metabolism* Humans Nuclear Proteins* Proto-Oncogene Proteins / genetics* Proto-Oncogene Proteins / physiology Proto-Oncogene Proteins c-mdm2 Tumor Cells, Cultured
IF 5.791
Times Cited 31
Human and Animal Cells U-87 MG(RCB0419)