PT  - JOURNAL ARTICLE
AU  - VERNON E. STEELE
AU  - JULIA T. ARNOLD
AU  - HANH LE
AU  - GRANT IZMIRLIAN
AU  - MARC R. BLACKMAN
TI  - Comparative Effects of DHEA and DHT on Gene Expression in Human LNCaP Prostate Cancer Cells
DP  - 2006 Sep 01
TA  - Anticancer Research
PG  - 3205--3215
VI  - 26
IP  - 5A
4099  - http://ar.iiarjournals.org/content/26/5A/3205.short
4100  - http://ar.iiarjournals.org/content/26/5A/3205.full
SO  - Anticancer Res2006 Sep 01; 26
AB  - Background: DHEA is widely used as a dietary supplement in older men. Because DHEA can be converted to androgens or estrogens, such use may promote prostate cancer. In this study, the effects of DHEA were compared with those of DHT using gene expression array profiles in human LNCaP prostate cancer cells. Materials and Methods: LNCaP cells were exposed to DHEA (300 nM), DHT (300 nM), or vehicle for 48 h, and mRNA expression was measured using Affymetrix HU-95 gene chips. Gene expression values were sorted in ascending order on the p-values corresponding to the extent of differential RNA expression between control and either hormone treatment. Results: S100 calcium binding protein, neurotensin, 24-dehydrocholesterol reductase, and anterior-gradient 2 homologue were the four most differentially expressed genes (p-values all <3×10-5). Nested tests of differential expression revealed lesser effects of DHEA versus DHT treatment (p<0.01) for the S100 calcium binding protein and neurotensin genes. Microarray findings were confirmed by QRT-PCR. The top 83 genes exhibiting differential expression after DHEA or DHT were used for pathway analysis. DHT decreased expression of more genes involved in intercellular communication, signal transduction, nucleic acid binding and transport, and in structural components, such as myosin and golgin, than DHEA. Conclusion: These data revealed consistent, measurable changes in gene expression patterns following treatment of LNCaP prostate cancer cells with DHEA and DHT. Understanding the mechanisms of DHEA versus DHT actions in the prostate may help clarify the separate and interactive effects of androgenic and estrogenic actions in prostate cancer progression. Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved