Alternative pathways to prostate carcinoma activate prostate stem cell antigen expression

Prostate Stem Cell Antigen (PSCA) is a glycosylphosphatidylinositol-anchore d cell surface protein that is expressed in normal human prostate and overe xpressed in human prostate cancers. To test whether different pathways that generate prostate cancer would affect PSCA expression, a murine model syst em was developed, Monoclonal antibodies were generated against murine PSCA (mPSCA), mPSCA is expressed on similar to 20% of cells in normal prostate e pithelium, and this number decreases dth increasing age. In the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of prostate cancer, tumo rs develop between 19 and 25 weeks of age, Murine PSCA was strongly express ed on similar to 60% of the cells of TRAMP tumors, at an age where the numb er of PSCA+ cells and the level of expression of PSCA is very low in the no rmal prostate. Phosphatase and tensin homologue deleted on chromosome 10 (P TEN) +/- mice develop a number of different canters, including prostate can cer. The incidence of prostate cancer is low and occurs after a relatively long latency, Fluorescence-activated cell sorter analysis of prostatic tiss ue from 11-18-month-old PTEN +/- mice shelved elevated numbers of PSCA+ cel ls in the prostate, and immunohistochemical analysis showed high mPSCA expr ession in the tumors of these mice, Together, these results show that two d istinct mechanisms of carcinogenesis lead to expression of a common target antigen.