Peroxisome proliferator-activated receptor γ regulates E-cadherin expression and inhibits growth and invasion of prostate cancer
Peroxisome proliferator-activated receptor γ regulates E-cadherin expression and inhibits growth and invasion of prostate cancer
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DOI：
10.1128/mcb.00605-06
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发表时间：
2006-10-01
影响因子：
5.3
通讯作者：
Fajas, Lluis
中科院分区：
文献类型：
--
作者：
Annicotte, Jean-Sebastien;Iankova, Irena;Fajas, Lluis
过氧化物酶体增殖物激活受体γ（PPAR γ）可能不允许前列腺癌细胞中的配体激活。PPART与抑制因子或PPAR γ蛋白翻译后修饰的相关性可以解释最近随机临床试验中PPAR-gamma配体缺乏作用的原因。使用细胞和前列腺癌异种移植小鼠模型，我们在这项研究中证明，使用PPAR-gamma激动剂吡格列酮和组蛋白去乙酰化酶抑制剂丙戊酸的联合治疗在抑制前列腺肿瘤生长方面比每种单独治疗更有效。我们表明，联合治疗会削弱小鼠前列腺癌细胞的骨侵袭潜力。此外，我们证明了在丙戊酸和吡格列酮的存在下，E-钙粘蛋白（一种参与细胞迁移和侵袭控制的蛋白质）的表达高度上调。我们发现，E-钙粘蛋白的表达只响应于组合治疗，而不是单一的PPAR-gamma激动剂，定义了一类新的PPAR-gamma靶基因。这些结果为前列腺癌的治疗开辟了新的治疗前景。
Peroxisome prolliferator-activated receptor gamma (PPAR gamma) might not be permissive to ligand activation in prostate cancer cells. Association of PPART with repressing factors or posttranslational modifications in PPAR,y protein could explain the lack of effect of PPAR-gamma ligands in a recent randomized clinical trial. Using cells and prostate cancer xenograft mouse models, we demonstrate in this study that a combination treatment using the PPAR-gamma agonist pioglitazone and the histone deacetylase inhibitor valproic acid is more efficient at inhibiting prostate tumor growth than each individual therapy. We show that the combination treatment impairs the bone-invasive potential of prostate cancer cells in mice. In addition, we demonstrate that expression of E-cadherin, a protein involved in the control of cell migration and invasion, is highly up-regulated in the presence of valproic acid and pioglitazone. We show that E-cadherin expression responds only to the combination treatment and not to single PPAR-gamma agonists, defining a new class of PPAR gamma target genes. These results open up new therapeutic perspectives in the treatment of prostate cancer.