AbstractBACKGROUNDRecent evidence suggests that prostate stem cells in benign and tumor tissue express the cell surface marker CD133, but these cells have not been well characterized. The aim of our study was to gene expression profile CD133‐expressing cells.METHODSWe analyzed CD133‐positive (CD133+) and ‐negative (CD133−) sub‐populations of high‐integrin expressing epithelial cells isolated from benign human prostate tissue and hormone‐refractory prostate cancer (HRPC).RESULTSCD133+ cells freshly isolated from benign prostate tissue exhibited an expression profile characteristic of a putative stem/progenitor cell population, with transcripts involved in biological processes ranging from development and ion homeostasis to cell communication. The profile of CD133− cells was consistent with that of a transit amplifying population, suggesting up‐regulated proliferation and metabolism. Comparison of benign populations to those from HRPC showed some similarities between CD133+ profiles but also revealed significant differences that provide a tumor‐specific pattern, which included evidence of increased metabolic activity and active proliferation. Subsequently, we demonstrated protein expression of a number of candidate genes in these cell populations and in benign tissue. In a novel observation we also found expression of some of these markers in prostate tumors, including the oligodendrocyte lineage transcription factor OLIG1.CONCLUSIONSThis study provides a unique genome‐wide molecular signature of CD133+ and CD133− human prostate epithelial cells. This will provide a valuable resource for prostate stem cell biology research and the identification of novel therapeutic targets for the treatment of prostate cancer. Prostate 68:1007–1024, 2008. © 2008 Wiley‐Liss, Inc.