Although prostate cancer initially responds and regresses in response to androgen-depletion therapy, most human prostate cancers will re-grow as an androgen-independent tumour. The goal of our study was to apply functional genomics to identify gene expression changes involved in this process. Two high-throughout technologies, cDNA microarrays and tissue micorarrays, were applied to explore the molecular mechanisms underlying hormone-refractory prostate cancer.

A cDNA microarray consisting of 6,048 transcripts was constructed (including 4,032 known genes, and 2,016 ESTs) and applied to the identification of differentially regulated genes between a panel of hormone-sensitive human prostate cancer xenografts (CWR22), and their hormone-refractory derivatives (CWR22R). A tumour tissue microarray1 with 269 clinical specimens (27 benign prostates, as well as 50 incidental, 138 clinically localized and 54 hormone-refractory recurrent cancers) was constructed to investigate whether candidate genes discovered by the cDNA microarray are also involved in vivo in human prostate cancer progression. For example, upregulation of one of such gene, insulin growth factor binding protein 2 (IGFBP2), was significantly (P<0.0001) associated with hormone-refractory tumours using the tissue array analysis. In conclusion, the combination of cDNA and tissue microarray analysis is a powerful strategy to identify novel cancer associated genes, and to rapidly explore their role in clinical prostate cancer.