Abstract Background We have investigated the involvement of renin-angiotensin system (RAS) in the development and progression of prostate cancer. Although the local RAS of prostate gland related to cell proliferation and angiogenesis has the potential in carcinogenesis of prostate, the detailed mechanism remains unclear. In the present study, we examined the effects of angiotensin 2 (Ang2) signal, especially through AT1 receptor (AT1R) in prostate cancer cells. Method Cell proliferations of prostate cancer, androgen dependent LNCaP and androgen independent DU145 cells, were examined after knocking down AT1R by AT1 small interfering RNA (siRNA) transfection. We confirmed the expression of AT1R, androgen receptor (AR) and its related proteins by Western blot analysis. Immunocytochemical staining of AR in LNCaP cells transfected with AT1R siRNA (LNCaP siRNA cells) was performed. We examined the promoter activities of AR and PSA in luciferase assay by transfection of AT1R siRNA. Result Cell proliferation of LNCaP siRNA and DU145 cells transfected with AT1R siRNA were decreased on 7 days by 75% and 52%, respectively. Western blot analysis showed the increase of cleaved PARP and survivin related to apoptosis. Interestingly, AR was dramatically suppressed in LNCaP siRNA cells. The flow cytometry of LNCaP siRNA cells showed G2 arrest or increase of apoptosis. In addition, PSA, COX2, NFκB, and c-myc expression were decreased in LNCaP siRNA cells. Luciferase assay showed that the activity of AR promoter or PSA promoter were inhibited by AT1R knocking down. In immunocytochemical staining, the suppression of AR translocation into nucleus by DHT was confirmed in LNCaP siRNA cells. Ang2 induced the cell proliferation associated with the enhancement of AR, PSA, and NFκB, and furthermore the activity of AR or PSA promoter. Discussion In this study, we focused on the involvement of RAS in the AR expression of prostate cancer cells. Knocking down AT1 receptor protein resulted in a significant inhibition of cell growth associated with a remarked decrease of AR protein. We also found that the expression level of AT1R could modulate the transcriptional level of AR by affecting c-myc and NFκB expression. Taken together, there seems to be a strong relationship between AR and Ang2-AT1R signals. These results indicate that the inhibition of AT1 receptor has a potential to influence the AR expression in prostate cells, presumably contributing to develop novel therapeutic agents for prostate cancer, especially hormone refractory cancer. 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 3187.