PROSTATE STEM-CELL ANTIGEN - A CELL-SURFACE MARKER OVEREXPRESSED IN PROSTATE-CANCER

The identification of cell surface antigens is critical to the develop ment of new diagnostic and therapeutic modalities for the management o f prostate cancer. Prostate stem cell antigen (PSCA) is a prostate-spe cific gene with 30% homology to stem cell antigen 2, a member of the T hy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell s urface antigens. PSCA encodes a 123-aa protein with an amino-terminal signal sequence, a carboxyl-terminal GPI-anchoring sequence, and multi ple N-glycosylation sites, PSCA mRNA expression is prostate-specific i n normal male tissues and is highly up-regulated in both androgen-depe ndent and -independent prostate cancer xenografts, In situ mRNA analys is localizes PSCA expression in normal prostate to the basal cell epit helium, the putative stem cell compartment of (he prostate, There is m oderate to strong PSCA expression in 111 of 126 (88%) prostate cancer specimens examined by in situ analysis, including high-grade prostatic intraepithelial neoplasia and androgen-dependent and androgen-indepen dent tumors. Flow cytometric analysis demonstrates that PSCA. is expre ssed predominantly on the cell surface and is anchor ed by a GPI linka ge. Fluorescent in situ hybridization analysis localizes the PSCA gene to chromosome 8q24.2, a region of allelic gain in more than 80% of pr ostate cancers. A mouse homologue with 70% amino acid identity and sim ilar genomic organization to human PSCA has also been identified. Thes e results support PSCA as a target for prostate cancer diagnosis and t herapy.