GKLF as a Novel Target in Selenium Chemoprevention of Prostate Cancer
Abstract
The present study investigated the functional significance of the zinc finger transcription factor gut-enriched kr ppel-like factor (GKLF) in mediating selenium action in the androgen receptor (AR)-null PC-3 human prostate cancer cells. We found that overexpression of GKLF enhances selenium inhibition of DNA synthesis and induction of apoptosis. Furthermore, knocking down the expression of GKLF greatly attenuates the growth suppressive and apoptosis inducing activities of selenium. Therefore, our data support an important role of GKLF induction in selenium action in the AR-null prostate cancer cells. However, we found that, in cells expressing a functional AR, the disruption of AR signaling is most likely more important than the induction of GKLF signaling for selenium action. Selenium treatment significantly decreases the expression of AR and AR-regulated genes implicated in prostate carcinogenesis (PSA, KLK2, ABCC4, DHCR24, and GUCY1A3) in five human prostate cancer cell lines irrespective of their AR genotype (wild-type vs. mutant) or sensitivity to androgen stimulated growth. Transfection of AR in the androgen-dependent LNCaP cells weakens significantly the inhibitory effect of selenium on cell proliferation and AR target gene expression. Since the vast majority of prostate cancers, including those refractory to hormone therapy, express a functional AR, the disruption of AR signaling is probably more important for selenium action and more relevant to selenium chemoprevention of prostate cancer than the induction of GKLF.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2008
- Accession Number
- ADA484722
Entities
People
- Yan Dong
Organizations
- Roswell Park Comprehensive Cancer Center