Suppression versus induction of androgen receptor functions by the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer LNCaP cells with different passage numbers
Suppression versus induction of androgen receptor functions by the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer LNCaP cells with different passage numbers
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DOI：
10.1074/jbc.m300676200
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发表时间：
2003-12-19
影响因子：
4.8
通讯作者：
Chang, CS
中科院分区：
文献类型：
--
作者：
Lin, HK;Hu, YC;Chang, CS
磷脂酰肌醇3-激酶（PI 3 K）/ Akt通路控制几种重要的生物学功能，如细胞生长调节、凋亡和迁移。然而，PI 3 K/ Akt控制雄激素受体（AR）介导的前列腺癌细胞生长的方式仍然不清楚且有争议。在这里，我们证明了PI 3 K/ Akt通路以细胞传代次数依赖性的方式调节AR活性。具体地，PI 3 K/ Akt通路可以抑制具有低传代次数的雄激素依赖性LNCaP细胞中的AR活性。相反，它还可以增强具有高传代次数的LNCaP细胞中的AR活性。此外，我们还证明胰岛素样生长因子-1可以激活PI 3 K/ Akt通路，导致AR在Ser（210）和Ser（790）处磷酸化。这些事件的结果可能会改变AR蛋白的稳定性。总之，我们的结果表明，PI 3 K/ Akt通路可能具有不同的机制来调节前列腺癌细胞各个阶段的AR功能，并且抗雄激素和抗PI 3 K/ Akt抑制剂的联合治疗可能值得考虑作为未来对抗前列腺癌的治疗方法。
The phosphatidylinositol 3- kinase ( PI3K)/ Akt pathway controls several important biological functions, such as cell growth regulation, apoptosis, and migration. However, the way in which PI3K/ Akt controls androgen receptor ( AR)- mediated prostate cancer cell growth remains unclear and controversial. Here, we demonstrate that the PI3K/ Akt pathway regulates AR activity in a cell passage number- dependent manner. Specifically, PI3K/ Akt pathway can suppress AR activity in androgen- dependent LNCaP cells with low passage numbers. In contrast, it can also enhance AR activity in LNCaP cells with high passage numbers. Furthermore, we also demonstrate that insulin- like growth factor- 1 can activate the PI3K/ Akt pathway that results in the phosphorylation of AR at Ser(210) and Ser(790). The consequence of these events may then change the stability of AR protein. Together, our results demonstrate that the PI3K/ Akt pathway may have distinct mechanisms to modulate AR functions in various stages of prostate cancer cells and that a combined therapy of antiandrogens and anti- PI3K/ Akt inhibitors may be worth considering as a future therapeutic approach to battle prostate cancer.