Effect of activator of G-protein signaling 3 (AGS3) on prostate tumorigenesis

Prostate cancer (PCa) is a leading cause of cancer death among men, with greater prevalence of the disease among the African American population in the US. Activator of G-protein Signaling 3 (AGS3/GPSM1), a receptor-independent activator of G-protein signaling has been shown to affect different cellular processes and cell cycle activity as well as tumor growth and development. AGS3 contains seven tetratricopeptide (TPR) repeats in its N-terminal half and four G-protein regulatory (GPR) motifs in its C-terminal half. The aim of this study is to assess the role of AGS3 in prostate cancer development and metastasis as well as to understand the molecular dynamics involved. To that end, the metastatic PCa cell lines LNCaP, PC3, MDA PCa 2b and DU-145 were analysed for AGS3 expression relative to RWPE-1, a non-metastatic Pca cell line. Quantitative RT-PCR and western blot analysis have shown that AGS3 expression varies in the PCa cell lines relative to control RWPE-1. Overexpression of AGS3 in PC3 and LNCaP cells significantly enhanced tumor progression in nude mice xenografts. Interestingly, expression of the TPR, not the GPR, repeats in LNCaP promoted tumor growth as well as the full length AGS3. Preliminary studies with a Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice deficient in AGS3 expression (TRAMP+/AGS3-/-) displayed decrease prostate tumorigenesis. Taken together, these results indicate that AGS3 expression promotes prostate tumor growth. The data also suggest that the effect of AGS3 in prostate tumorigenesis is mediated via its TPR, not GPR motif. Citation Format: Timothy O. Adekoya, Nikia Smith, Tonelia Mowatt, Temilade Aladeniyi, Ricardo M. Richardson. Effect of activator of G-protein signaling 3 (AGS3) on prostate tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5745.