MDR1, chemotherapy and chromatin remodeling.
The development of multidrug resistance (MDR) in cancer can severely impede the efficacy of chemotherapy treatment. P-glycoprotein (Pgp) overexpression, encoded by the MDR1 gene, is a well-established mediator of MDR. MDR1 expression is rapidly upregulated by chemotherapeutic drugs and a number of other exogenous stimuli, however the mechanisms underlying its transcriptional regulation remain unclear. In recent years, research has indicated that chromatin accessibility, or epigenetic modifications, will play a large role in controlling the endogenous MDR1 expression state, and its response to activation stimuli. This review examines some of these studies, and discusses how new developments from the greatly expanding epigenetics field may extend to MDR1 transcriptional research.
Epigenetics in Human Health and Disease Laboratory, Baker Heart Research Institute, Alfred Medical Research and Education Precinct (AMREP), Prahran, Victoria, Australia.
Emma K
EK
Baker
Assam
A
El-Osta
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002843:Chromatin / Q000378:metabolism*; D019175:DNA Methylation; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D010641:Phenotype; D014158:Transcription, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002843:Chromatin