Comparison of protein expression in two prostate cancer cell-lines, LNCaP and DU145, after treatment with somatostatin
Comparison of protein expression in two prostate cancer cell-lines, LNCaP and DU145, after treatment with somatostatin
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生长抑素处理后两种前列腺癌细胞系 LNCaP 和 DU145 中蛋白质表达的比较
DOI：
10.3892/or_00000587
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发表时间：
2009-12-01
期刊：
影响因子：
4.2
通讯作者：
Holmberg, Anders R.
中科院分区：
文献类型：
--
作者：
Liu, Zhaoxu;Marquez, Marcela;Holmberg, Anders R.
人们对前列腺癌进展的潜在机制知之甚少。对雄激素有反应的蛋白质可能参与前列腺癌的发展和进展以及雄激素消融治疗的最终失败。生长抑素（sms）类似物治疗可能是激素难治性前列腺癌患者化疗的一种可能的替代治疗方法。我们使用两种前列腺癌细胞系，LNCaP（雄激素依赖性）和DU 145（雄激素非依赖性），比较蛋白质表达。两种细胞系都用sins及其衍生物smsdx处理。Smsdx是一种糖基化的聚sms，具有很高的稳定性，适合临床使用。蛋白质表达的比较研究通过二维凝胶电泳（2DE），然后通过质谱分析进行了分析。与对照细胞相比，在sms/smsdx处理的LNCaP和DU 145细胞中的蛋白质表达谱中观察到显著的定量差异。三分之一的检测到的蛋白质差异表达（PRDXs，hnRNP，HSP，RKIP）。在smsdx和sms处理的细胞之间观察到蛋白质表达模式的一致性，在蛋白质的上调和下调之间具有很强的一致性。鉴定了58个（49种蛋白质的同种型）蛋白质点，发现LNCaP和DU 145细胞之间差异表达为2倍变化。LNCaP中有31种蛋白质的表达高于DU 145。DU 145中有27个蛋白的表达高于LNCaP。LNCaP和DU 145细胞之间的大多数差异表达蛋白（2倍）受到sms/smsdx处理的影响（1.2- 2.6倍变化）。Sms/smsdx影响前列腺癌细胞的线粒体，最终触发线粒体介导的凋亡。某些蛋白质的调节（例如，RKIP，VDACs）的表达，提示sms/smsdx对前列腺癌细胞的作用是通过MAPK途径和调节磷酸酪氨酸磷酸酶活性实现的。
The mechanisms underlying prostate cancer progression are poorly understood. Proteins responsive to androgens may be involved in the development and progression of prostate cancer and the ultimate failure of androgen-ablation therapy. Therapy with somatostatin (sms) analogues could be a possible therapeutic alternative to chemotherapy in hormone refractory prostate cancer patients. We used two prostate cancer cell-lines, LNCaP (androgen-dependent) and DU145 (androgen-independent), to compare the protein expressions. Both cell lines were treated with sins and its derivative smsdx. Smsdx is a glycosylated poly sms with high stability suitable for clinical use. A comparison study of protein expression was analyzed by means of two-dimensional gel electrophoresis (2DE) followed by mass spectrometric analysis. Marked quantitative differences were observed in the protein expression profiles in sms/smsdx treated LNCaP and DU145 cells compared to the control cells. One third of the detected proteins were differentially expressed (PRDXs, hnRNPs, HSPs, RKIP). Concordance in protein expression patterns was observed between smsdx and sms treated cells with strong agreement between the up- and down-regulation of proteins. Fifty-eight (isoforms of 49 proteins) protein spots were identified and found differentially expressed at 2-fold change between LNCaP and DU145 cells. Thirty-one proteins in LNCaP have higher expressions than in DU145. Twenty-seven proteins in DU145 have higher expressions than in LNCaP. Most of the differentially expressed proteins (2-fold) between LNCaP and DU145 cells were affected by sms/smsdx treatment (1.2- to 2.6-fold change). Sms/smsdx affects the mitochondria of prostate cancer cells in a way that eventually triggers mitochondrial-mediated apoptosis. Regulation of certain proteins (e.g., RKIP, VDACs) by sms/smsdx suggests that sms/smsdx exerts its effects on prostate cancer cells via MAPK pathway and by regulating the activities of phosphotyrosine phosphatases.