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Updated: May 20, 2026

Cholesterol Efflux Assay
Published on: March 6, 2012
The response of the prostate to circulating cholesterol: activating transcription factor 3 (ATF3) as a prominent node
Jayoung Kim1, Dolores Di Vizio, Taek-Kyun Kim
1Division of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. Jayoung.Kim@cshs.org
Abstract:
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.
Insights
High cholesterol impacts prostate health by altering gene expression and cell proliferation. This study identifies ATF3 as a key regulator in the prostate's response to cholesterol, offering new insights into prostate health.
Area of Science:
- Molecular biology
- Cell biology
- Bioinformatics
Background:
- Elevated circulating cholesterol is a known risk factor for cardiovascular disease and metabolic syndrome.
- The prostate's response to cholesterol level variations is not well understood.
Purpose of the Study:
- To investigate the molecular and cellular effects of altered cholesterol levels on the normal prostate.
- To identify key molecular players and pathways involved in cholesterol sensing in the prostate.
Main Methods:
- Integrated bioinformatic analysis of DNA microarray data from mice with high cholesterol and human prostate cells with cholesterol depletion.
- Construction of a cholesterol-sensitive gene expression network.
- Validation experiments to assess ATF3 expression and prostate cell proliferation.
Main Results:
- A cholesterol-sensitive gene network was constructed, highlighting ATF3 as a key node.
- Elevated cholesterol reduced ATF3 expression and increased prostate cell proliferation.
- Cholesterol depletion increased ATF3 levels and inhibited proliferation.
- In vivo cholesterol reduction decreased periprostatic inflammation.
Conclusions:
- ATF3 acts as a cholesterol sensor in the prostate, regulating cell proliferation.
- Cholesterol levels significantly influence prostate molecular and cellular functions.
- Findings provide novel insights into cholesterol's role in prostate health and disease.
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