Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate Cancer
Abstract
The present study is to investigate the functional significance and mechanism of selenium suppression of hTERT in human prostate cancer. We found that over-expression of hTERT attenuates the apoptosis inducing activities of selenium, supporting an important role of hTERT in selenium action in prostate cancer cells. More importantly, we found that combined bicalutamide (an anti-androgen) and selenium treatment further decreases AR transcriptional activity, hTERT expression and induces greater apoptosis than single treatment alone, indicating that selenium in combination with anti-androgen could represent a viable approach to improve the therapeutic outcome of androgen deprivation therapy. We also found that selenium can induce DNA damage response in LNCaP cells. In addition, our data showed that androgen-stimulated AR signaling induces the expression of hTERT through up-regulating hTERT promoter activity. Selenium can block the induction of hTERT by androgen, suggesting that AR signaling is mediating the inhibitory effect of selenium on hTERT expression. However, over-expression of AR is not able to reverse the effect of selenium on hTERT expression. The data indicate that in addition to change of AR protein level, other mechanism(s) might involve in this process. Additionally, we found that prostate cancer cells expressing wild-type or mutant AR respond differentially to androgen in term of hTERT expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2009
- Accession Number
- ADA519540
Entities
People
- Shuang Liu
Organizations
- Tulane University of Louisiana