Steele Vernon E, Arnold Julia T, Lei Hanh, Izmirlian Grant, Blackman Marc R
Endocrine Section, Laboratory of Clinical Investigation, Division of Intramural Research, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 20892, USA.
Anticancer Res. 2006 Sep-Oct;26(5A):3205-15.
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.
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.
S100 calcium binding protein, neurotensin, 24-dehydrocholesterol reductase, and anterior-gradient 2 homologue were the four most differentially expressed genes (p-values all < 3 x 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.
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.
脱氢表雄酮（DHEA）在老年男性中被广泛用作膳食补充剂。由于DHEA可转化为雄激素或雌激素，这种用途可能会促进前列腺癌。在本研究中，利用人LNCaP前列腺癌细胞中的基因表达阵列谱，比较了DHEA与双氢睾酮（DHT）的作用。
将LNCaP细胞暴露于DHEA（300 nM）、DHT（300 nM）或溶剂中48小时，使用Affymetrix HU-95基因芯片测量mRNA表达。根据与对照和任一激素处理之间RNA差异表达程度对应的p值，将基因表达值按升序排序。
S100钙结合蛋白、神经降压素、24-脱氢胆固醇还原酶和前梯度2同源物是四个差异表达最显著的基因（p值均<3×10⁻⁵）。差异表达的嵌套检验显示，对于S100钙结合蛋白和神经降压素基因，DHEA处理与DHT处理相比作用较小（p<0.01）。通过定量逆转录聚合酶链反应（QRT-PCR）证实了微阵列结果。对DHEA或DHT处理后表现出差异表达的前83个基因进行通路分析。与DHEA相比，DHT降低了更多参与细胞间通讯、信号转导、核酸结合与转运以及结构成分（如肌球蛋白和高尔基体蛋白）的基因表达。
这些数据揭示了用DHEA和DHT处理LNCaP前列腺癌细胞后基因表达模式一致且可测量的变化。了解DHEA与DHT在前列腺中的作用机制可能有助于阐明雄激素和雌激素作用在前列腺癌进展中的单独和交互作用。
