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A PSCA Promoter Based Avian Retroviral Transgene Model of Normal and Malignant Prostate
Annual rept. 1 Apr 2004-31 Mar 2005
CALIFORNIA UNIV LOS ANGELES
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The molecular and cellular origins of prostate cancer are poorly understood. Recent evidence from our laboratory suggests that prostate cancer may arise from a basalluminal precursor cell marked by cell surface expression of PSCA. The evidence supporting this hypothesis is that 1 PSCA marks an intermediate cell population that co-expresses basal and luminal cell cytokeratins 2 this cell population is does not express p63 and is androgen receptor positive, all hallmarks of prostate cancer, and 3 PSCA is highly expressed in HGPIN and prostate cancer and in all animal models of prostate cancer. To test this hypothesis and to develop new models of prostate, we propose to determine whether delivery of oncogenes specifically to the PSCA positive cells of mouse prostate is sufficient to cause cancer. To accomplish this, we will develop a transgenic mouse model in which the retroviral receptor gene tva is expressed in the prostate under control of the PSCA promoter. Virus containing one or more oncogenes will be delivered to the prostate and the resulting phenotype characterized.
APPROVED FOR PUBLIC RELEASE