PloS one, 2012-07, Vol.7 (7), p.e39448-e39448
2012
Details
- Autor(en) / Beteiligte
- Titel
- The response of the prostate to circulating cholesterol: activating transcription factor 3 (ATF3) as a prominent node in a cholesterol-sensing network
- Ist Teil von
- PloS one, 2012-07, Vol.7 (7), p.e39448-e39448
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Elevated circulating cholesterol is a systemic risk factor for cardiovascular disease and metabolic syndrome, however the manner in which the normal prostate responds to variations in cholesterol levels is poorly understood. In this study we addressed the molecular and cellular effects of elevated and suppressed levels of circulating cholesterol on the normal prostate. Integrated bioinformatic analysis was performed using DNA microarray data from two experimental formats: (1) ventral prostate from male mice with chronically elevated circulating cholesterol and (2) human prostate cells exposed acutely to cholesterol depletion. A cholesterol-sensitive gene expression network was constructed from these data and the transcription factor ATF3 was identified as a prominent node in the network. Validation experiments confirmed that elevated cholesterol reduced ATF3 expression and enhanced proliferation of prostate cells, while cholesterol depletion increased ATF3 levels and inhibited proliferation. Cholesterol reduction in vivo alleviated dense lymphomononuclear infiltrates in the periprostatic adipose tissue, which were closely associated with nerve tracts and blood vessels. These findings open new perspectives on the role of cholesterol in prostate health, and provide a novel role for ATF3, and associated proteins within a large signaling network, as a cholesterol-sensing mechanism.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0039448Titel-ID: cdi_plos_journals_1325027900
- Format
- –
- Schlagworte
- Activating transcription factor 3, Activating Transcription Factor 3 - biosynthesis, Adipose tissue, Adipose Tissue - metabolism, Analysis, Animals, Anticholesteremic agents, Antigens, B cells, Bioengineering, Biology, Blood vessels, Cardiovascular diseases, Cell Line, Tumor, Cell Proliferation, Chemical engineering, Chemistry, Cholesterol, Cholesterol - blood, Colorectal cancer, Deoxyribonucleic acid, Departments, Depletion, Disease, DNA, DNA microarrays, Gene expression, Gene Expression Profiling, Genes, Health risks, Hospitals, Humans, Inflammation, Interdisciplinary aspects, Male, Medical schools, Medicine, Metabolic syndrome, Metabolism, Mice, Mice, SCID, Oligonucleotide Array Sequence Analysis - methods, Pathogenesis, Pharmacology, Prostate, Prostate - metabolism, Prostate cancer, Proteins, Risk factors, Signal transduction, Signal Transduction - physiology, Signaling, Surgery, Transcription factors, Urogenital system