GKLF as a Novel Target in Selenium Chemoprevention of Prostate Cancer
Abstract
The present study examined the mechanistic basic for selenium upregulation of the zinc finger transcription factor gut-enriched krueppel-like factor (GKLF) and the effect of GKLF overexpression on the growth of prostate cancer cells. The studies were conducted in the androgen-responsive LNCaP and the androgen-unresponsive, AR-null PC 3 cells. We found that selenium upregulates GKLF transcript through distinct mechanisms in the two cell types: a decrease in mRNA degradation in LNCap and an increase in GKLF transcription in PC-3. Transfection of GKLF in PC-3 cells inhibited DNA synthesis and induced apoptosis. In contrast, LNCaP cells responded to GKLF transfection by increasing the level of androgen receptor (AR), and the effect of which predominated, leading to a modest stimulation of cell growth. We also found that selenium significantly decreases the expression of AR in LNCaP cells. Exogeneous expression of AR greatly attenuated the growth suppressive activity of selenium, although the GKLF level was markedly induced after the transfection. Therefore, compared to the induction of GKLF, the disruption of AR signaling is probably more important for selenium action and more relevant to selenium chemoprevention of prostate cancer, since the vast majority of prostate cancers, including those refractory to hormone therapy, express a functional AR.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA434843
Entities
People
- Yan Dong
Organizations
- Roswell Park Comprehensive Cancer Center