STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors

In search of novel genes expressed in metastatic prostate cancer, we subtra cted cDNA isolated from benign prostatic hypertrophic tissue from cDNA isol ated from a prostate cancer xenograft model that mimics advanced disease. O ne novel gene that is highly expressed in advanced prostate cancer encodes a 339-amino acid protein with six potential membrane-spanning regions flank ed by hydrophilic amino- and carboxyl-terminal domains. This structure sugg ests a potential function as a channel or transporter protein. This gene, n amed STEAP for six-transmembrane epithelial antigen of the prostate, is exp ressed predominantly in human prostate tissue and is up-regulated in multip le cancer cell lines, including prostate, bladder, colon, ovarian, and Ewin g sarcoma. Immunohistochemical analysis of clinical specimens demonstrates significant STEAP expression at the cell-cell junctions of the secretory ep ithelium of prostate and prostate cancer cells. Little to no staining was d etected at the plasma membranes of normal, nonprostate human tissues, excep t for bladder tissue, which expressed low levels of STEAP at the cell membr ane. Protein analysis located STEAP at the cell surface of prostate-cancer cell lines. Our results support STEAP as a cell-surface tumor-antigen targe t for prostate cancer therapy and diagnostic imaging.