Troglitazone increases expression of E-cadherin and claudin 4 in human pancreatic cancer cells
Troglitazone increases expression of E-cadherin and claudin 4 in human pancreatic cancer cells
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DOI：
10.1016/j.bbrc.2009.01.134
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发表时间：
2009-03-13
影响因子：
3.1
通讯作者：
Okumura, Toshikatsu
中科院分区：
文献类型：
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作者：
Kumei, Shima;Motomura, Wataru;Okumura, Toshikatsu
我们检测了曲格列酮对人胰腺癌细胞E-cadherin和claudin 4表达的影响。曲格列酮剂量依赖性地增加k -1细胞E-cadherin和claudin 4mrna和蛋白的表达。蜗牛、蛞蝓和ZEB1的mrna未被曲格列酮改变，说明这三种转录抑制物不会在曲格列酮诱导E-cadherin中发挥作用。GW9662是一种PPAR γ拮抗剂，无法阻断E-cadherin或claudin 4mrna的表达，提示PPAR γ非依赖性通路。MEK抑制剂U0126增加E-cadherin或claudin 4mrna和蛋白的表达，并有效抑制细胞侵袭。由于我们之前的研究显示曲格列酮下调MEK-ERK信号，抑制细胞侵袭pk1，这些结果提示曲格列酮可能通过抑制胰腺癌细胞中MEK-ERK信号而增加E-cadherin和claudin 4的表达，这可能与曲格列酮诱导的细胞侵袭活性抑制有关。(C) 2009爱思唯尔公司版权所有。
We examined the effects of troglitazone on expression of E-cadherin and claudin 4 in human pancreatic cancer cells. Troglitazone dose-dependently increased expression of E-cadherin and claudin 4 mRNA and protein in PK-1 cells. Snail, Slug and ZEB1, mRNAs were not changed by troglitazone, indicating that these three transcriptional repressors Would not play a role in the induction of E-cadherin by troglitazone. GW9662, a PPAR gamma antagonist, failed to block the increased expression of E-cadherin or claudin 4 mRNA, Suggesting a PPAR gamma-independent pathway. A MEK inhibitor, U0126, increased E-cadherin or claudin 4 mRNA and protein expression, and potently inhibited cell invasion. Because troglitazone down-regulates MEK-ERK signaling and inhibit cell invasion in PK-1 as shown in our previous study, these results suggest that troglitazone increases expression of E-cadherin and claudin 4 possibly through inhibition of MEK-ERK signaling in pancreatic cancer cells, which might be involved in the troglitazone-induced inhibition of cell invasive activity. (C) 2009 Elsevier Inc. All rights reserved.