Biomarkers of Selenium Chemoprevention of Prostate Cancer
Abstract
The present study examined the cellular and molecular effects of selenium in the androgen-responsive LNCaP cells. Physiological concentrations of selenium produced a dose- and time-dependent inhibition of growth with this cell line. An arrest at 00/G1 phase was observed at 24 h. A marked decrease in the transcript and protein level of androgen receptor (AR) and prostate-specific antigen was detected as early as 6 b, suggesting that the interference of androgen signaling by selenium is not a consequence of growth arrest. Additional experiments showed that selenium was capable of suppressing the DNA-binding and the trans-activating activity of AR. Gene expression profiling was carried out in order to identify other AR-targets responsive to selenium modulation. The analysis showed that selenium was able to countermand the expression of a subset of 12 additional AR-regulated genes. These genes all contain ARE motifs in their promoters. As a follow-up to the above investigation, we also found that selenium favorably altered the expression of 12 putative oncogenes, tumor-suppressor genes, or genes implicated in the transformation to androgen-independency. By extracting relevant information from the microarray data, we have thus uncovered a number of potentially exciting clues regarding the action of selenium in prostate cancer prevention.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA423294
Entities
People
- Yan Dong
Organizations
- Health Research, Incorporated