Open AccessTranscriptional regulation of breast cancer resistance protein
Author(s) -
Xiaochang Wu,
Shubin Peng,
Qian Huang
Publication year - 2012
Publication title -
yichuan
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 16
ISSN - 0253-9772
DOI - 10.3724/sp.j.1005.2012.01529
Subject(s) - transcription factor , biology , aryl hydrocarbon receptor , nuclear receptor , ap 1 transcription factor , cancer research , estrogen related receptor gamma , enhancer , microbiology and biotechnology , genetics , gene
Breast cancer resistance protein (BCRP), also known as ABCG2, is a member of the ATP-binding cassette (ABC) transporter superfamily, and is known to play important roles in cancer multidrug resistance. The BCRP promoter lacks a TATA-box and contains a CAAT-box, lots of AP1, AP2 sites and several putative Sp1 sites which are downstream of a putative CpG island. Several transcription factors, such as progesterone receptor (PR), estrogen receptor (ER), nuclear factor-κB (NF-κB), hypoxia-inducible factors (HIFs), nuclear factor erythroid 2-related factor 2 (Nrf2), aryl hydrocarbon receptor (AhR), peroxisome proliferator-activated receptors (PPARs) and Krüppel-like factor 5 (KLF5), have been recently shown to bind to their response elements in the promoter/enhancer to activate the transcription of BCRP. BCRP transcription can be influenced by proinflammatory cytokines, growth factors, and homeobox protein MSX2. Signaling pathways, such as Sonic hedgehog (Shh), Notch and RAR/RXR pathways, may also involve in the transcriptional regulation of BCRP. In addition, promoter methylation and histone acetylation are essential for the BCRP transcription, especially for the drug-induced BCRP expression. This paper reviews the recent research progresses in this field with an emphasis on the roles of transcription factors and epigenetics in the transcriptional regulation of BCRP.