Transcriptional regulation of MDR genes

The emergence of resistance in a tumor population is most often associated with a disregulation of gene expression, usually at the level of transcription. A major goal in the field of cancer chemotherapy is to define the mechanisms underlying transcriptional regulation of drug resistance genes in an...

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Bibliographic Details
Published inCytotechnology (Dordrecht) Vol. 27; no. 1-3; pp. 257 - 269
Main Authors Scotto, K W, Egan, D A
Format Journal Article
LanguageEnglish
Published United States Springer Nature B.V 01.09.1998
Kluwer Academic Publishers
Subjects
Cell differentiation
Chemotherapy
Drug resistance
Environmental effects
Gene expression
Gene regulation
Genes
Molecular modelling
Multidrug resistance
P-Glycoprotein
Transcription
Tumor cells
Tumors
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Summary:The emergence of resistance in a tumor population is most often associated with a disregulation of gene expression, usually at the level of transcription. A major goal in the field of cancer chemotherapy is to define the mechanisms underlying transcriptional regulation of drug resistance genes in an effort to identify targets for therapeutic intervention. Recently, considerable progress has been made in identifying the molecular mechanisms involved in the transcriptional regulation of the P-glycoprotein (Pgp) gene. When overexpressed in tumor cells, Pgp confers resistance to a variety of chemotherapeutic agents; this resistance has been termed MDR (multidrug resistance). Moreover, Pgp is a normal component of a variety of highly differentiated cell types and, as such, is regulated by both internal and external environmental stimuli. In this review, we will discuss the current knowledge regarding the DNA elements and protein factors involved in both constitutive and inducible regulation of Pgp transcription in normal and tumor cells.
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ISSN:0920-9069
1573-0778
DOI:10.1023/A:1008032716628