STEAP1 exepression in prostate cancer and its regulation by androgens

• Main Author: Gomes, Inês Margarida Amaral Santos
• Publication Date: 2010
• Format: Master thesis
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: http://hdl.handle.net/10400.6/2853
• topic: Cancro da prostata; Androgénios

Six transmembrane epithelial antigen of the prostate 1 (STEAP1) was identified as a gene overexpressed in human prostate cancer and spontaneous transgenic mouse model of prostate cancer. It is localized in cell junctions of epithelial cells, and its structure with six transmembrane domains, suggests that it may act as a membrane channel or transporter protein in tight junctions, gap junctions or in cell adhesion, helping in intercellular communication in a way that allows growth of cancer cells. Although STEAP1 expression seems to be up-regulated in all stages of prostate cancer, its clinical significance remains to be clarified. Moreover, STEAP1 is more expressed in LNCaP than in PC3, suggesting that androgens may regulate its expression. Therefore, the goals of this experimental work were: i) to evaluate if STEAP1 expression correlates with clinical reports from patients; ii) to analyze if STEAP1 is regulated by 5α- dihydrotestosterone (DHT) in vitro and in vivo, by Real-time PCR and Western blot. Immunohistochemical analysis revealed that STEAP1 expression is principally associated with epithelial cells, but it is also present in some stromal cells. Analysis of STEAP1 immunoreactivity in prostate cancer is underway. In vitro results demonstrated that both STEAP1 mRNA and protein expression are down-regulated in the presence of 1nM or 10nM DHT after 24h of stimulation. However, at least one more experimental assay is required to confirm these results. In vivo results demonstrated that castration visibly increases STEAP1 protein expression when compared to intact rats, and treatment with DHT abrogates the effect of castration in STEAP1 expression, suggesting that STEAP1 protein is down-regulated by DHT. However, these results do not correlate with STEAP1 mRNA expression, suggesting that mechanisms at the translation level may be involved