Abstract 1241: in Vivo Analysis of the Role of Lyn Tyrosine Kinase in Castrate-Resistant LNCaP Xenograft Tumor Growth

Introduction: It is proposed that advanced Prostate Cancer (PCa) tumors develop mechanisms, which re-activate the androgen receptor (AR) axis via oncogenic pathways, in which tyrosine kinases play a crucial role. Genetic manipulation of several tyrosine kinases in vivo revealed that only a knockout of Lyn tyrosine Kinase, compromised prostate gland development suggesting that Lyn plays a critical role in the regulation of AR in normal prostate development. Our results demonstrated that Lyn kinase enhances AR transcriptional activity and promotes prostate cancer cell survival. Thus, we hypothesized that Lyn kinase overexpression accelerates castrate-resistant LNCaP tumor growth and serum PSA relapse to pre-castration levels. Method: LNCaP cells stably overexpressing Lyn kinase (LNCaP Lyn ) or Empty vector (LNCap Empty ) were generated using clonal selection. 1 × 10 6 LNCaP Lyn and LNCaP Empty were injected into the male nude mice. Serum PSA level and tumor volumes were followed weekly and mice were castrated when serum PSA values reached 50ng/ml. Results: Interestingly, a higher rate of tumor growth and PSA relapse was observed after casteration in mice bearing the LNCaP Lyn compare to the LNCap Empty -bearing mice. Total protein was extracted from the xenograft tumors and levels of AR, PSA, FKBP52, AKT, pAKT were analyzed. Results of Protein analysis further confirmed the role of Lyn kinase in prostate cancer cell survival and progression to castrate resistant stage. Conclusion: Together, these results suggest that Lyn plays a key role in CRPC development and that inhibiting Lyn expression could be considered as a potential therapeutic target for CRPC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1241. doi:1538-7445.AM2012-1241