Identification of Tumor and Invasion Suppressor Gene Modulators in Bladder Cancer by Different Classes of Histone Deacetylase Inhibitors Using Reverse Phase Protein Arrays
Identification of Tumor and Invasion Suppressor Gene Modulators in Bladder Cancer by Different Classes of Histone Deacetylase Inhibitors Using Reverse Phase Protein Arrays
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DOI：
10.1016/j.juro.2010.02.004
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发表时间：
2010-06-01
影响因子：
6.6
通讯作者：
Summerhayes, Ian C.
中科院分区：
文献类型：
--
作者：
Gould, Justin J.;Kenney, Patrick A.;Summerhayes, Ian C.
目的：用反相蛋白质阵列技术研究不同组蛋白脱乙酰酶抑制剂对膀胱癌细胞系肿瘤和侵袭抑制基因的靶向作用。材料和方法：将三种低、中、高侵袭性组蛋白脱乙酰酶抑制剂曲古抑素A、APICIDIN、丙戊酸(Sigma(R))和MS-275(AXXORA(R))作用0~36h。裂解产物被收获并排列成10倍稀释系列，一式两份。结果：所有组蛋白去乙酰酶抑制剂、apicidin和MS-275分别作用于高侵袭性细胞株和中、高侵袭性细胞株，其蛋白表达谱分别显示高侵袭性细胞株和中、高侵袭性细胞株的α-连环素表达上调。在暴露于所有组蛋白脱乙酰酶抑制剂后，明胶蛋白在弱侵袭性和中等侵袭性品系中表达上调。4种组蛋白去乙酰化酶抑制剂均可下调低、中侵袭性细胞系中桥粒芯糖蛋白的表达，并降低中高侵袭性细胞株FAX的表达。结论：不同类型的组蛋白去乙酰化酶抑制物具有调节肿瘤和侵袭抑制基因表达的作用，可作为膀胱癌的潜在治疗药物。反向蛋白质阵列能够高通量筛选多个化合物，以评估特定的治疗蛋白质组的表达谱。
Purpose: We assessed the ability of different classes of histone deacetylase inhibitors to target tumor and invasive suppressor genes in a panel of bladder carcinoma cell lines using reverse phase protein arrays.Materials and Methods: Three poorly, moderately and highly invasive cell lines were exposed to histone deacetylase inhibitors, trichostatin A, apicidin, valproic acid (Sigma (R)) and MS-275 (AXXORA (R)) for 0 to 36 hours. Lysates were harvested and arrayed in a 10-fold dilution series in duplicate. Data points were collected and analyzed using a concentration interpolation methodology after normalization.Results: Protein expression profiles revealed up-regulation of gamma-catenin in highly invasive lines, and alpha-catenin in moderately and highly invasive lines after exposure to all histone deacetylase inhibitors, apicidin and MS-275, respectively. Gelsolin was up-regulated in poorly and moderately invasive lines after exposure to all histone deacetylase inhibitors. Desmoglein was down-regulated in poorly and moderately invasive cell lines by all 4 histone deacetylase inhibitors, in addition to decreased FAX (Transduction Laboratories (TM)) expression in moderately and highly invasive lines exposed to valproic acid and MS-275.Conclusions: Different histone deacetylase inhibitor classes have the potential to modulate tumor and invasive suppressor gene expression, identifying histone deacetylase inhibitors as potential therapeutic agents for bladder cancer. Reverse phase protein arrays enable high throughput screening of multiple compounds to assess the expression profile of specific protein groups targeted for therapy.