New Insights in Prostate Cancer Development and Tumor Therapy: Modulation of Nuclear Receptors and the Specific Role of Liver X Receptors.

Abstract

Prostate cancer (PCa) incidence has been dramatically increasing these last years in westernized countries. Though localized PCa is usually treated by radical prostatectomy, androgen deprivation therapy is preferred in locally advanced disease in combination with chemotherapy. Unfortunately, PCa goes into a castration-resistant state in the vast majority of the cases, leading to questions about the molecular mechanisms involving the steroids and their respective nuclear receptors in this relapse. Interestingly, liver X receptors (LXRα/NR1H3 and LXRβ/NR1H2) have emerged as new actors in prostate physiology, beyond their historical roles of cholesterol sensors. More importantly LXRs have been proposed to be good pharmacological targets in PCa. This rational has been based on numerous experiments performed in PCa cell lines and genetic animal models pointing out that using selective liver X receptor modulators (SLiMs) could actually be a good complementary therapy in patients with a castration resistant PCa. Hence, this review is focused on the interaction among the androgen receptors (AR/NR3C4), estrogen receptors (ERα/NR3A1 and ERβ/NR3A2), and LXRs in prostate homeostasis and their putative pharmacological modulations in parallel to the patients' support.

• Authors: Laura Bousset, Amandine Rambur, Allan Fouache, Julio Bunay, Laurent Morel, Jean-Marc A Lobaccaro, Silvère Baron, Amalia Trousson, Cyrille de Joussineau
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 9 (Aug 28 2018) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30154328 (Publication Type: Journal Article, Review)

Chemical References

• Androgens
• Endocrine Disruptors
• Estrogens
• Liver X Receptors
• Oxysterols
• Receptors, Cytoplasmic and Nuclear

Topics

• Androgens (metabolism)
• Animals
• Cell Transformation, Neoplastic (genetics, immunology, metabolism)
• Disease Management
• Endocrine Disruptors (adverse effects)
• Environmental Exposure (adverse effects)
• Estrogens (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Lipid Metabolism
• Liver X Receptors (genetics, metabolism)
• Male
• Neovascularization, Pathologic (immunology, metabolism)
• Oxysterols (metabolism)
• Prostate (metabolism, pathology)
• Prostatic Neoplasms (diagnosis, etiology, metabolism, therapy)
• Receptors, Cytoplasmic and Nuclear (metabolism)
• Signal Transduction