TY - JOUR
T1 - Transcription factor-mediated regulation of the BCRP/ABCG2 efflux transporter
T2 - a review across tissues and species
AU - Gorczyca, Ludwik
AU - Aleksunes, Lauren M.
N1 - Funding Information:
This work was supported by the National Institutes of Health–National Institute of Environmental Health Sciences [grant numbers T32ES007148, R01ES029275, R01ES021800, R01GM123330, F31ES029794, and P30ES005022]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/3/3
Y1 - 2020/3/3
N2 - Introduction: The breast cancer resistance protein (BCRP/ABCG2) is a member of the ATP-binding cassette superfamily of transporters. Using the energy garnered from the hydrolysis of ATP, BCRP actively removes drugs and endogenous molecules from the cell. With broad expression across the liver, kidney, brain, placenta, testes, and small intestines, BCRP can impact the pharmacokinetics and pharmacodynamics of xenobiotics. Areas covered: The purpose of this review is to summarize the transcriptional signaling pathways that regulate BCRP expression across various tissues and mammalian species. We will cover the endobiotic- and xenobiotic-activated transcription factors that regulate the expression and activity of BCRP. These include the estrogen receptor, progesterone receptor, peroxisome proliferator-activated receptor, constitutive androstane receptor, pregnane X receptor, nuclear factor e2-related factor 2, and aryl hydrocarbon receptor. Expert opinion: Key transcription factors regulate BCRP expression and function in response to hormones and xenobiotics. Understanding this regulation provides an opportunity to improve pharmacotherapeutic outcomes by enhancing the efficacy and reducing the toxicity of drugs that are substrates of this efflux transporter.
AB - Introduction: The breast cancer resistance protein (BCRP/ABCG2) is a member of the ATP-binding cassette superfamily of transporters. Using the energy garnered from the hydrolysis of ATP, BCRP actively removes drugs and endogenous molecules from the cell. With broad expression across the liver, kidney, brain, placenta, testes, and small intestines, BCRP can impact the pharmacokinetics and pharmacodynamics of xenobiotics. Areas covered: The purpose of this review is to summarize the transcriptional signaling pathways that regulate BCRP expression across various tissues and mammalian species. We will cover the endobiotic- and xenobiotic-activated transcription factors that regulate the expression and activity of BCRP. These include the estrogen receptor, progesterone receptor, peroxisome proliferator-activated receptor, constitutive androstane receptor, pregnane X receptor, nuclear factor e2-related factor 2, and aryl hydrocarbon receptor. Expert opinion: Key transcription factors regulate BCRP expression and function in response to hormones and xenobiotics. Understanding this regulation provides an opportunity to improve pharmacotherapeutic outcomes by enhancing the efficacy and reducing the toxicity of drugs that are substrates of this efflux transporter.
KW - ABCG2
KW - Breast Cancer Resistance Protein (BCRP)
KW - transcription
KW - transporter
UR - http://www.scopus.com/inward/record.url?scp=85081747047&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081747047&partnerID=8YFLogxK
U2 - 10.1080/17425255.2020.1732348
DO - 10.1080/17425255.2020.1732348
M3 - Review article
C2 - 32077332
AN - SCOPUS:85081747047
SN - 1742-5255
VL - 16
SP - 239
EP - 253
JO - Expert Opinion on Drug Metabolism and Toxicology
JF - Expert Opinion on Drug Metabolism and Toxicology
IS - 3
ER -