Sex steroid-induced DNA methylation changes and inflammation response in prostate cancer |
| |
| Institution: | 1. Department of Gastroenterology and Hepatology, Erasmus MC – University Medical Center Rotterdam, The Netherlands;2. Liver Clinic University Health Network, Division of Gastroenterology, University of Toronto, Canada;1. Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25 rue Dr Roux, 75015 Paris, France;2. INSERM U955, AP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, Créteil, France;1. Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona, Italy;2. Division of Gastroenterology, Azienda Ospedaliero Universitaria “Ospedali Riuniti”, Ancona, Italy;3. Epidemiology Unit, Centro Studi Fegato, Trieste, Italy;4. Servizio di Gastroenterologia - Ospedale “Ramazzini” Carpi, Modena, Italy;5. Institute of Pathologic Anatomy, Università Politecnica delle Marche, Ancona, Italy;6. Division of Cytopathology, Azienda Ospedaliero Universitaria “Ospedali Riuniti”, Ancona, Italy;7. Division of Gastroenterology and Digestive Endoscopy, Università degli Studi di Bologna, Castel San Pietro Terme Hospital, Castel San Pietro Terme, Italy;1. Inserm Unit 976, Hospital Saint-Louis and Université Paris Diderot, Sorbonne Paris Cité, Laboratory UMRS 976, Paris, France;2. Inserm Unit 976, Hospital Saint-Louis and Université Paris Diderot, Sorbonne Paris Cité, Laboratory UMRS 976, Paris, France;3. Inserm Unit 976, Hospital Saint-Louis and Université Paris Diderot, Sorbonne Paris Cité, Laboratory UMRS 976, Paris, France;4. Inserm Unit 976, Hospital Saint-Louis and Université Paris Diderot, Sorbonne Paris Cité, Laboratory UMRS 976, Paris, France;5. Inserm Unit 976, Hospital Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité, Laboratory UMRS 976, and Department of Dermatology, Assistance Publique–Hôpitaux de Paris, Hospital Saint-Louis, Paris, France;1. Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Nordre Fasanvej 57, 2000 Frederiksberg, Denmark;2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 9609 Medical Center Drive, MSC 9774, Bethesda, MD 20892-9774, USA;3. Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, 1. Floor, 2100 Copenhagen Ø, Denmark |
| |
| Abstract: | BackgroundSex steroid hormones have been reported to induce inflammation causing dysregulation of cytokines in prostate cancer cells. However, the underlying epigenetic mechanism has not well been studied. The objective of this study was to evaluate the effect of sex steroid hormones on epigenetic DNA methylation changes in prostate cancer cells using a signature PCR methylation array panel that correspond to 96 genes with biological function in the human inflammatory and autoimmune signals in prostate cancer. Of the 96-gene panel, 32 genes showed at least 10% differentially methylation level in response to hormonal treatment when compared to untreated cells. Genes that were hypomethylated included CXCL12, CXCL5, CCL25, IL1F8, IL13RAI, STAT5A, CXCR4 and TLR5; and genes that were hypermethylated included ELA2, TOLLIP, LAG3, CD276 and MALT1. Quantitative RT-PCR analysis of select genes represented in a cytokine expression array panel showed inverse association between DNA methylation and gene expression for TOLLIP, CXCL5, CCL18 and IL5 genes and treatment of prostate cancer cells with 5′-aza-2′-deoxycytidine with or without trichostatin A induced up-regulation of TOLLIP expression. Further analysis of relative gene expression of matched prostate cancer tissues when compared to benign tissues from individual patients with prostate cancer showed increased and significant expression for CCL18 (2.6-fold; p < 0.001), a modest yet significant increase in IL5 expression (1.17-fold; p = 0.015), and a modest increase in CXCL5 expression (1.4-fold; p = 0.25). In conclusion, our studies demonstrate that sex steroid hormones can induce aberrant gene expression via differential methylation changes in prostate carcinogenesis. |
| |
| Keywords: | DNA methylation Sex steroid hormones Inflammation and prostate cancer |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
