Abstract 3251: Zebrafish: Is it a viable model for prostate cancer

Abstract

Abstract Since its introduction as a vertebrate model organism for developmental studies, the Zebrafish model has continued to improve in its useful applications for studying human disease and more recently cancer. However, because there has been no evidence for the presence of prostate glands in fish, this model has not been exploited to study cancer of the prostate gland. In this abstract, we present evidence that fish carry prostate-like cells and, therefore, we postulate that zebrafish could be used as a model for prostate cancer research. We hypothesized that even though a well-defined prostate gland is not present in fish, there may be a few cells similar to thyroid gland. As a first approach, we developed an experimental design for detection of Prostate Specific Antigen (PSA) gene and protein expression, as well as PSA gene mapping. PSA is a serine protease that binds in seminal plasma to protein C inhibitor, which is involved in the clotting cascade in humans. When we analyzed the zebrafish genome, we found a PSA gene that is syntenic to human PSA and at the protein level zebrafish PSA is 70% homologous to human PSA. We also found PSA mRNA by RT-PCR analysis of the total testes RNA. In situ hybridization of the 4 day old zebrafish larva revealed expression of PSA in gonad. Treatment of zebrafish larvae with the anti-androgen, hydroxyl-flutamide, showed a PSA response profile similar to that in mammalian models in which there is a reduction in PSA mRNA at low doses and an increase at high doses with a return to baseline levels. Based on these findings we contend zebrafish have cells which are functionally equivalent to the prostate gland. We further believe that this information supports the notion of using zebrafish as a model to generate prostate cancer -like symptoms and propose for future studies expression of SV40 large T antigen under the PSA promoter to be used to demonstrate proof of principle. Such a model would be useful to explore not only early detection of prostate cancer but also to provide the opportunity for large scale studies of chemical suppression of cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3251.