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首页> 外文期刊>Cell cycle >Thiazolidinediones regulate expression of cell cycle proteins in human prostate cancer cells via PPARgamma-dependent and PPARgamma-independent pathways.
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Thiazolidinediones regulate expression of cell cycle proteins in human prostate cancer cells via PPARgamma-dependent and PPARgamma-independent pathways.

机译：噻唑烷二酮类通过PPARγ依赖性和PPARγ依赖性途径调节人前列腺癌细胞中细胞周期蛋白的表达。

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Thiazolidinediones (TZDs) are peroxisome proliferator activated receptor gamma (PPARgamma) ligands that have been reported to reduce proliferation of human prostate cancer cells. However, the mechanisms by which TZDs inhibit prostate cancer cell proliferation are not fully understood. In addition, it is not known if the anti-proliferative effects of TZDs require activation of PPARgamma or are mediated by PPARgamma-independent pathways. The goals of this study were to assess whether TZDs regulate expression of proteins that control the transition from G1 to S phase of the cell cycle and define the role of PPARgamma in these TZD-induced responses in androgen-independent human prostate cancer cell lines. Western blot analysis revealed that growth inhibitory concentrations of the TZDs rosiglitazone and ciglitazone induced expression of the cyclin dependent kinase inhibitor p21 and decreased cyclin D1 levels in the androgen independent PC-3 cell line. Phosphorylation of retinoblastoma protein at Serine 780 was also reduced in PC-3 cells exposed to ciglitazone. Furthermore, growth inhibitory concentrations of ciglitazone increased p21 and lowered cyclin D1 expression within C4-2 cells. PPARgamma-directed siRNAs inhibited the ability of rosiglitazone to regulate expression of cyclin D1 and p21. However, knockdown of PPARgamma did not significantly reduce ciglitazone-induced alterations in cyclin D1 and p21. Furthermore PPARgamma siRNA did not prevent inhibition of PC-3 cell proliferation by either TZD. Thus, activation of PPARgamma is involved in rosiglitazone-induced alterations in cell cycle protein expression. However, the alterations in protein expression and proliferation induced by ciglitazone occur primarily via PPARgamma-independent signaling pathways.
机译：噻唑烷二酮（TZD）是过氧化物酶体增殖物激活的受体γ（PPARgamma）配体，据报道可减少人类前列腺癌细胞的增殖。但是，TZDs抑制前列腺癌细胞增殖的机制尚未完全了解。此外，尚不清楚TZD的抗增殖作用是否需要激活PPARgamma或是否由PPARgamma依赖性途径介导。这项研究的目的是评估TZD是否调节控制细胞周期从G1到S期过渡的蛋白质表达，并确定PPARgamma在这些TZD诱导的雄激素非依赖性人类前列腺癌细胞系中的作用。蛋白质印迹分析显示，TZDs罗格列酮和西格列酮的生长抑制浓度诱导雄激素非依赖性PC-3细胞株中细胞周期蛋白依赖性激酶抑制剂p21的表达，并降低细胞周期蛋白D1的水平。在暴露于西格列酮的PC-3细胞中，视网膜母细胞瘤蛋白在780号丝氨酸上的磷酸化也降低了。此外，西格列酮的生长抑制浓度增加了C4-2细胞内的p21并降低了细胞周期蛋白D1的表达。 PPARγ指导的siRNA抑制罗格列酮调节cyclin D1和p21表达的能力。但是，PPARgamma的敲除并没有显着减少西格列酮诱导的细胞周期蛋白D1和p21的改变。此外，PPARgamma siRNA不能阻止任何TZD抑制PC-3细胞增殖。因此，PPARγ的激活与罗格列酮诱导的细胞周期蛋白表达改变有关。但是，西格列酮诱导的蛋白质表达和增殖的改变主要通过不依赖PPARγ的信号传导途径发生。

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