Gene expression profiling reveals novel targets of estramustine phosphate in prostate cancer cells

Estramustine phosphate (EMP) is a compound widely used for the treatment of hormone-refractory prostate cancer. In order to better understand the precise molecular mechanism(s) by which EMP exerts its effects on hormone-resistant PC3 prostate cancer cells, we have utilized microarray to interrogate 22,215 known genes to determine the gene expression profiles altered by EMP treatment. The purpose of this investigation was to identify gene expression profile first and then in future studies determine the specific role of these genes in EMP-induced apoptosis in prostate cancer cells. We found a total of 726 genes which showed > 2 fold change after EMP treatment. Clustering analysis showed 12 different types of expression alteration. These genes were also subjected to cluster analysis according to their biological functions. We found that EMP regulated the expression of genes, which are critically involved in the regulation of cell growth, cell cycle, apoptosis, iron homeostasis, cyloskeleton and cell signaling transduction, Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to confirm the results of microarray, and the results of real-time quantitative RT-PCR were consistent with the microarray data. From these results, we conclude that EMP caused changes in the expression of a large number of genes that are related to the control of cell survival and physiological behaviors. The gene expression profiles may provide comprehensive molecular mechanism(s) by which EMP exerts its pleiotropic effects on prostate cancer cells. EMP-induced regulation of these genes may be further exploited for devising therapeutic strategies for prostate cancer. (C) 2004 Elsevier Ltd. All rights reserved.