Deciphering Beta-Catenin Contributions in Prostate Cance

前列腺癌是北美男性癌症相关死亡的第二大原因。在 大多数情况下，PrCa变得雄激素非依赖性(Al)或激素难治性。向Al进军 PRCA是多因素的，可归因于循环激活有利于生存的细胞信号 生长因子、雄激素受体(AR)异常转录和逃避细胞凋亡。我们已经展示了 研究表明，癌蛋白Beta-catenin可以改变AR的转录，并可能有助于 Al PrCa期间的异常生长。我们还表明，肿瘤抑制因子PTEN可以对 调节β-连环蛋白/Tcf信号转导。利用函数系统的损失和增益，我们提出了进一步 评估β-连环蛋白在PrCA中的作用。具体地说，前列腺特异性PTEN基因敲除小鼠将允许 美国评估β-连环蛋白和已知调节其活性的分子的表达和分布。 我们还将使用在可诱导的TET下稳定地转导PTEN的LNCaP PrCa细胞 受调控的启动子。这些细胞的生长和PSA分泌将被评估为携带 异种移植物。这些新的活体工具将使我们能够理解β-连环蛋白在Al PrCa中的作用。

Prostate cancer (PrCa) is the second leading cause of cancer related death in North American men. In the majority of cases, PrCa becomes androgen-independent (Al)or hormone refractory. Progression to Al PrCa is multi-factorial and can be attributed to activation of pro-survival cell signalling by circulating growth factors, aberrant androgen receptor (AR) transcription and evasion of apoptosis. We have shown shown that the oncoprotein, Beta-catenin, can alter AR transcription and potentially contribute towards aberrant growth during Al PrCa. We have also shown that the tumour suppressor, PTEN, can negatively regulate Beta-catenin/Tcf signalling. Using both loss and gain of function systems we proposed to further evaluate the role of Beta-catenin in PrCa. Specifically, a prostate specific PTEN knock-out mouse will allow us to evaluate expression and distribution of Beta-catenin and molecules known to regulate its activity. We will also employ the use of LNCaP PrCa cells stably transfected with PTEN under an inducible Tet regulated promoter. These cells will be assessed for growth and PSA secretion in tumours carried as xenografts. These novel in vivo tools will allow understanding to the role of Beta-catenin has in Al PrCa.