Publication: Pregnane X receptor and human malignancy
Authors
Koutsounas, Ioannis ; Patsouris, Efstratios ; Theocharis, Stamatios E.
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Pregnane X Receptor (PXR) is a member of
the nuclear receptor superfamily, expressed in liver,
intestine and other tissues. PXR exerts transcriptional
regulation by binding to its DNA response elements as
an heterodimer with Retinoid X Receptor (RXR). This
nuclear receptor is implicated in the homeostasis of
numerous endobiotics, such as glucose, lipids, steroids
and bile acids. Additionally, the activation of PXR
induces expression of drug metabolizing enzymes
(DMEs) and transporters, including multidrug resistance
protein 1 (MDR1), leading to regulation of xenobiotic
metabolism and drug-drug interactions. New roles for
PXR have been established in inflammatory bowel
disease, bone homeostasis, liver steatosis, antifibrogenesis
and oxidative stress. PXR has, additionally, a
multifactorial impact on cancer, either by directly
affecting cell proliferation and apoptosis or by inducing
chemotherapy resistance, in colon, breast, prostate, and
endometrial cancer, and in osteosarcoma. PXR
polymorphisms may also have clinical significance in
certain types of cancer and their treatment. Further
studies are needed in order to clarify the mechanisms
involved in PXR-regulated carcinogenesis. PXR downregulation
could be considered as a novel therapeutic
approach to overcome chemoresistance, while future
research should be mainly focused on modulating PXR
status in order to increase chemotherapy effectiveness
and finally improve cancer patient prognosis.
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Citation
Histology and histopathology, Vol. 28, n.º 4 (2013)
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