Functional characterization of peroxisome proliferator-activated receptor-β/δ expression in colon cancer.
Functional characterization of peroxisome proliferator-activated receptor-β/δ expression in colon cancer.
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DOI：
10.1002/mc.20757
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发表时间：
2011-11
影响因子：
4.6
通讯作者：
Peters, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Foreman, Jennifer E.;Chang, Wen-Chi L.;Palkar, Prajakta S.;Zhu, Bokai;Borland, Michael G.;Williams, Jennie L.;Kramer, Lance R.;Clapper, Margie L.;Gonzalez, Frank J.;Peters, Jeffrey M.
本研究严格检查了PPARβ/δ在结肠癌模型中的作用。人结肠腺癌组织中PPARβ/δ mRNA和蛋白的表达低于相应的非转化组织，而CYCLIN D1蛋白的表达高于相应的非转化组织。与对照组织相比，在来自Apc+/Min-FCCC小鼠的结肠肿瘤中观察到类似的结果。Apc+/Min-FCCC小鼠经饮食给予舒林酸对正常结肠组织或结肠肿瘤中的PPARβ/δ表达无影响。在已知可增加细胞凋亡的条件下，在与PPARβ/δ配体GW 0742一起培养的人结肠癌细胞系中，切割的聚（ADP-核糖）聚合酶（PARP）增加或不变，而14-3-3ε的表达不受影响。虽然DLD 1细胞在用过氧化氢处理后，在配体激活PPARβ/δ后表现出较少的早期凋亡细胞，但这种变化与晚期凋亡/坏死细胞的增加有关，但与活细胞的增加无关。在人结肠癌细胞系中稳定过表达的PPARβ/δ增强了HT 29细胞中PPARβ/δ的配体活化和克隆形成的抑制。这些研究是迄今为止最定量的研究，证明了人和Apc+/Min-FCCC小鼠结肠肿瘤中的PPARβ/δ表达低于相应的正常组织，这与人结肠癌细胞系中PPARβ/δ表达和活化增加抑制克隆形成的发现一致。由于配体诱导的早期凋亡减弱可能与更多晚期凋亡/坏死细胞相关，但与更多活细胞无关，因此这些研究说明了未来需要对PPARβ/δ依赖性凋亡调节进行更全面分析的原因。
This study critically examined the role of PPARβ/δ in colon cancer models. Expression of PPARβ/δ mRNA and protein was lower and expression of CYCLIN D1 protein higher in human colon adenocarcinomas compared to matched non-transformed tissue. Similar results were observed in colon tumors from Apc+/Min-FCCC mice compared to control tissue. Dietary administration of sulindac to Apc+/Min-FCCC mice had no influence on expression of PPARβ/δ in normal colon tissue or colon tumors. Cleaved poly (ADP-ribose) polymerase (PARP) was either increased or unchanged, while expression of 14-3-3ε was not influenced in human colon cancer cell lines cultured with the PPARβ/δ ligand GW0742 under conditions known to increase apoptosis. While DLD1 cells exhibited fewer early apoptotic cells after ligand activation of PPARβ/δ following treatment with hydrogen peroxide, this change was associated with an increase in late apoptotic/necrotic cells, but not an increase in viable cells. Stable over-expression of PPARβ/δ in human colon cancer cell lines enhanced ligand activation of PPARβ/δ and inhibition of clonogenicity in HT29 cells. These studies are the most quantitative to date to demonstrate that expression of PPARβ/δ is lower in human and Apc+/Min-FCCC mouse colon tumors than in corresponding normal tissue, consistent with the finding that increasing expression and activation of PPARβ/δ in human colon cancer cell lines inhibits clonogenicity. Because ligand-induced attenuation of early apoptosis can be associated with more late, apoptotic/necrotic cells, but not more viable cells, these studies illustrate why more comprehensive analysis of PPARβ/δ-dependent modulation of apoptosis is required in the future.
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影响因子：
3.6
作者：
Liou, Jun-Yang;Wu, Chia-Ching;Wu, Kenneth K.
通讯作者：
Wu, Kenneth K.
DOI：
10.1161/01.atv.0000223875.14120.93
发表时间：
2006-07-01
影响因子：
8.7
作者：
Liou, Jun-Yang;Lee, Sang;Wu, Kenneth K.
通讯作者：
Wu, Kenneth K.
影响因子：
11.2
作者：
Liou, Jun-Yang;Ghelani, Dipak;Wu, Kenneth K.
通讯作者：
Wu, Kenneth K.
影响因子：
3.5
作者：
Leibowitz, MD;Fiévet, C;Auwerx, J
通讯作者：
Auwerx, J
影响因子：
5.8
作者：
Bogazzi, F;Ultimieri, F;Martino, E
通讯作者：
Martino, E