Deciphering Beta-Catenin Contributions in Prostate Cance

前列腺癌（PrCa）是北美男性癌症相关死亡的第二大原因。在 在大多数情况下，PrCa成为雄激素非依赖性（Al）或激素难治性。进展到Al PrCa是多因素的，并且可以归因于通过循环免疫抑制剂激活促存活细胞信号传导。 生长因子、异常雄激素受体（AR）转录和凋亡逃避。我们已经表明 研究表明，癌蛋白β-连环蛋白可以改变AR的转录，并可能有助于 在Al PrCa期间的异常生长。我们还发现，肿瘤抑制因子PTEN可以负性地 调节β-连环蛋白/Tcf信号传导。使用函数系统的损失和增益，我们提出进一步 评估β-连环蛋白在PrCa中的作用。具体地，前列腺特异性PTEN敲除小鼠将允许 我们评估β-连环蛋白和已知调节其活性的分子的表达和分布。 我们还将使用在诱导型泰特诱导下用PTEN稳定转染的LNCaP PrCa细胞。 调控启动子将评估这些细胞在携带的肿瘤中的生长和PSA分泌， 异种移植这些新的体内工具将允许理解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.