Comprehensive analyses of prostate gene expression: Convergence of expressed sequence tag databases, transcript profiling and proteomics

Several methods nave been developed for the comprenensive analysts or gene expression in complex biological systems. Generally these procedures assess either a portion of the cellular transcriptome or a portion of the cellula r proteome. Each approach has distinct conceptual and methodological advant ages and disadvantages. We have investigated the application of both method s to characterize the gene expression pathway mediated by androgens and the androgen receptor in prostate cancer cells. This pathway is of critical im portance for the development and progression of prostate cancer. Of clinica l importance, modulation of androgens remains the mainstay of treatment for patients with advanced disease. To facilitate global gene expression studi es we have first sought to define the prostate transcriptome by assembling and annotating prostate-derived expressed sequence tags (ESTs). A total of 55 000 prostate ESTs were assembled into a set of 15 953 clusters putativel y representing 15 953 distinct transcripts. These clusters were used to con struct cDNA microarrays suitable for examining the androgen-response pathwa y at the level of transcription. The expression of 20 genes was found to be induced by androgens. This cohort included known androgen-regulated genes such as prostate-specific antigen (PSA) and several novel complementary DNA s (cDNAs). Protein expression profiles of androgen-stimulated prostate canc er cells were generated by two-dimensional electrophoresis (2-DE). Mass spe ctrometric analysis of androgen-regulated proteins in these cells identifie d the metastasis-suppressor gene NDKA/nm23, a finding that may explain a ma rked reduction in metastatic potential when these cells express a functiona l androgen receptor pathway.