Role of Peroxisome Proliferator-Activated Receptor β/δ and B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells.
Role of Peroxisome Proliferator-Activated Receptor β/δ and B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells.
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DOI：
10.1155/2013/121956
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发表时间：
2013
期刊：
影响因子：
2.9
通讯作者：
Vanden Heuvel JP
中科院分区：
文献类型：
--
作者：
Coleman JD;Thompson JT;Smith RW 3rd;Prokopczyk B;Vanden Heuvel JP
PPARβ/δ 是一种配体激活的转录因子，可通过直接诱导靶基因或与其相关的转录阻遏蛋白 BCL-6 协同调节各种细胞功能。基质重塑蛋白酶在胰腺癌中经常过度表达并与转移有关。本研究检验了以下假设：PPARβ/δ 在人胰腺癌细胞中表达，其激活可以调节 MMP-9，降低癌细胞穿过基底膜的能力。在人胰腺癌组织中，MMP-9和PPARβ/δ的表达显着升高，而BCL-6 mRNA的表达显着降低。在细胞培养模型中，PPARβ/δ 激活减少了 TNFα 诱导的各种与转移有关的基因的表达，并减少了通过基底膜的侵袭。通过使用 PPARβ/δ、BCL-6 和 MMP-9 的短发夹 RNA 抑制剂，很明显 PPARβ/δ 负责配体依赖性效应，而 GW501516 处理后 BCL-6 解离最终负责降低 MMP-9 表达，从而降低侵袭活性。这些结果表明，PPARβ/δ 通过配体依赖性 BCL-6 释放来调节基因，从而在调节胰腺癌细胞侵袭中发挥作用，并且受体的激活可能为控制迁移和转移提供另一种治疗方法。
PPARβ/δ is a ligand-activated transcription factor that regulates various cellular functions via induction of target genes directly or in concert with its associated transcriptional repressor, BCL-6. Matrix remodeling proteinases are frequently over-expressed in pancreatic cancer and are involved with metastasis. The present study tested the hypothesis that PPARβ/δ is expressed in human pancreatic cancer cells and that its activation could regulate MMP-9, decreasing cancer cells ability to transverse the basement membrane. In human pancreatic cancer tissue there was significantly higher expression of MMP-9 and PPARβ/δ, and lower levels of BCL-6 mRNA. PPARβ/δ activation reduced the TNFα-induced expression of various genes implicated in metastasis and reduced the invasion through a basement membrane in cell culture models. Through the use of short hairpin RNA inhibitors of PPARβ/δ, BCL-6, and MMP-9, it was evident that PPARβ/δ was responsible for the ligand-dependent effects whereas BCL-6 dissociation upon GW501516 treatment was ultimately responsible for decreasing MMP-9 expression and hence invasion activity. These results suggest that PPARβ/δ plays a role in regulating pancreatic cancer cell invasion through regulation of genes via ligand-dependent release of BCL-6 and that activation of the receptor may provide an alternative therapeutic method for controlling migration and metastasis.
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DOI：
10.1016/s0006-291x(02)02983-2
发表时间：
2003-01-31
影响因子：
3.1
作者：
Farrow, B;Evers, BM
通讯作者：
Evers, BM
影响因子：
2.9
作者：
Kawa, S;Nikaido, T;Kiyosawa, K
通讯作者：
Kiyosawa, K
细胞因子和信号通路调节角膜上皮细胞中基质金属蛋白酶 9 (MMP-9) 的表达。
影响因子：
5.6
作者：
Gordon, Gabriel M.;Ledee, Dolena R.;Feuer, William J.;Fini, M. Elizabeth
通讯作者：
Fini, M. Elizabeth
DOI：
10.1007/s12015-008-9024-2
发表时间：
2008-12-01
期刊：
STEM CELL REVIEWS
影响因子：
--
作者：
Cimini, AnnaMaria;Ceru, Maria Paola
通讯作者：
Ceru, Maria Paola
影响因子：
2.1
作者：
Goldstein, D;Carroll, S;Keogh, G
通讯作者：
Keogh, G