Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate Cancer
Abstract
The project is to investigate telomerase as a potential target of AR signaling suppression by selenium. We found that overexpression 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 combination of selenium and bicalutamide produce a robust down-regulation of androgen receptor (AR) signaling, hTERT expression and telomerase activity. Furthermore, apoptosis induction by the two agents is more significant compared to single treatment. Our findings thus indicate that selenium in combination with anti-androgen cold represent a viable approach to improve the therapeutic outcome of androgen deprivation therapy. Our date showed that selenium can induce DNA damage response in LNCaP cells. AR-mediated selenium suppression of hTERT expression is at transcriptional level. In addition, we found that wild-type and mutant AR response differentially to androgen under normoxia condition. However, in hypoxia condition, androgen up-regulates hTERT expression in both wild-type AR expression cells and mutant AR expressing cells. Selenium either alone or in combination with bicalutamide is able to inhibit androgen induced hTERT expression under hypoxia condition.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2011
- Accession Number
- ADA554036
Entities
People
- Shuang Liu
Organizations
- Tulane University of Louisiana