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Transcriptional Regulation of the Human MDR 1 Gene at the Level of the Inverted MED‐1 Promoter Region
Author(s) -
LABIALLE STEPHANE,
GAYET LANDRY,
MARTHINET ERIC,
RIGAL DOMINIQUE,
BAGGETTO LORIS G.
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb04685.x
Subject(s) - gene , promoter , transcriptional regulation , multiple drug resistance , transfection , biology , microbiology and biotechnology , regulatory sequence , activator (genetics) , inverted repeat , sequence (biology) , regulation of gene expression , genetics , gene expression , cancer research , drug resistance , genome
A bstract : The typical multidrug resistance phenotype (MDR), the major cause of failure of cancer chemotherapy, is the result of the overexpression of the human MDR 1 gene, the regulation of which is still incompletely understood. Using several EMSA experiments, we have identified a new regulatory sequence located from −103 to −98 bp relative to the +1 start site in the MDR 1 promoter region. This sequence, which we called inverted MED‐1, acts as a cis ‐activator for this gene. In transient transfection experiments of highly resistant human lymphoblastic CEM/VLB5 cells, its deletion from the promoter region is responsible for 60% inhibition of the MDR 1 transcriptional activity. This sequence specifically binds a nuclear protein of about 150–160 kDa. We showed that its binding capacity is related to the chemoresistance level of the studied cell lines and may reflect the increased transcriptional activity of the MDR 1 gene in multidrug‐resistant cells.