Identification of differentially expressed genes in organ-confined prostate cancer by gene expression array

BACKGROUND. To understand the molecular mechanisms underlying prostate canc er we have utilized the gene expression array to search for genes whose exp ression is altered in this disease. METHODS. RNA quality from manual microdissected tissue was compared with th at from microselected tissue by electrophoresis. For array analysis, malign ant and normal prostate epithelium was enriched using microselection techni que from prostate cancer and the peripheral zone of a normal prostate. Iden tical array membrane was hybridized to labeled cancer and normal cDNA, resp ectively. The differentially expressed gene was further evaluated by RT-PCR . RESULTS. Microdissection, but not microselection, causes visible degradatio n to RNA. Of the 588 genes on the membrane, 87 genes yielded significant si gnals. Based on a three fold difference relative to normal prostate tissue, 1 gene was overexpressed and 12 genes underexpressed in prostate cancer. O f them, five showed statistically significant reduction in mRNA levels in s ix prostate cancer specimens compared with seven normal prostate specimens. These five genes are glutathione S-transferase M1 (GSTM1), monocyte chemot actic protein-1 (MCP-1), tumor necrosis factor-alpha receptor-1 (TNFR-1), t ransforming growth factor beta3 (TGF-beta3), and inhibitor of DNA binding-1 (ID-1). CONCLUSIONS. GST-based metabolism, cytokine MCP-1 and TNFR-1, and TGF-beta3 signaling pathways, and some helix-loop-helix nuclear proteins could he po tentially important in organ-confined prostate cancer and deserve further i nvestigation. Prostate 47:132-140, 2001. (C) 2001 Wiley-Liss, Inc.