Expression of the PXR gene in various types of cancer and drug resistance

Abstract

Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. PXR is a key xenobiotic receptor that regulates the expression of genes implicated in drug metabolism, detoxification and clearance, including drug metabolizing enzymes and transporters, suggesting that it is significant in the drug resistance of cancer cells. PXR is expressed in a wide range of tissues in the human body. Studies have demonstrated that PXR is expressed in a variety of tumor types, correlating not only with drug resistance but also with the cell proliferation, apoptosis and prognosis of cancer. The purpose of the present review is to provide a comprehensive review of PXR and its potential roles in multidrug resistance and the biological characteristics of PXR-positive tumors.

Keywords: cancer; multidrug resistance; pregnane X receptor; tumor cell apoptosis.

Figure 1

Schematic comparison of the domain structures of a typical nuclear receptor and PXR. AF-1, activation function-1; DBD, DNA-binding domain; H, hinge region; LBD, ligand-binding domain; AF-2, transactivation function-2; PXR, pregnane X receptor.

Figure 2

Structure of the PXR LBD. The three-dimensional structure of the human PXR LBD is presented as a ribbon diagram. The α-helices, β-sheets and the AF-2 helix are indicated. The helix 1-helix 3 insert, which is unique to PXR among the NRs, is indicated in dark grey. The large solvent-accessible ligand-binding pocket is outlined in white. PXR, pregnane X receptor; LBD, ligand-binding domain; AF-2, transactivation function-2; NR, nuclear receptor. This figure is taken from ref. .