Selective activation of PPARγ in breast, colon, and lung cancer cell lines
Selective activation of PPARγ in breast, colon, and lung cancer cell lines
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DOI：
10.1016/j.mce.2005.02.003
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发表时间：
2005-05-12
影响因子：
4.1
通讯作者：
Kilgore, MW
中科院分区：
文献类型：
--
作者：
Allred, CD;Kilgore, MW
过氧化物酶体增殖物激活受体γ（PPAR γ）在几种癌症类型（包括乳腺癌、结肠癌和肺癌）的发展和进展中起着关键的作用，尽管定义不明确。利用PPAR应答元件（PPRE）报告基因测定来评价10种不同细胞系（包括正常乳腺上皮细胞、乳腺癌细胞、肺癌细胞和结肠癌细胞）中PPAR γ的选择性反式激活。用四种化合物之一处理细胞，所述化合物包括罗格列酮（Ros）、西格列酮（Cig）、15-脱氧-δ（12，14）-前列腺素J（2）（PGJ（2））或GW 9662（GW）。我们观察到来自不同组织来源的细胞系之间、来自单一组织类型的细胞系之间的反式激活的差异，以及不同配体在单一细胞系内对PPAR γ的选择性调节。有趣的是，GW，一种脂肪细胞中的PPAR γ拮抗剂，增强了正常乳腺上皮细胞中的PPRE报告基因激活，而它在任何测试的癌细胞系中几乎没有作用。在每种癌症类型中，发现单个细胞系对不同的PPAR γ配体的反应不同。例如，Ros、Cig和PGJ 2都是肺腺癌细胞系中PPAR γ反式激活的有效激动剂，而这些相同的配体在肺的鳞状细胞癌或大细胞癌中没有作用。PPARgamma与RXRa的比率预测了在三种测试的细胞系中的两种中细胞对Ros和9-顺式-视黄酸（一种RXR α激动剂）的共同处理的反应。这些数据表明，PPARgamma可以被选择性地调节，并表明它可以用作个体肿瘤的治疗靶点。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a critical albeit poorly defined role in the development and progression of several cancer types including those of the breast, colon, and lung. A PPAR response element (PPRE) reporter assay was utilized to evaluate the selective transactivation of PPAR gamma in 10 different cell lines including normal mammary epithelia], breast, lung, and colon cancer cells. Cells were treated with one of four compounds including rosglitizone (Ros), ciglitizone (Cig), 15-deoxy-Delta(12,14)-prostaglandin J(2) (PGJ(2)), or GW 9662 (GW). We observed differences in transactivation between cell lines from different tissue origin, across cell lines from a single tissue type, and selective modulation of PPAR gamma within a single cell line by different ligands. Interestingly, GW, a PPAR gamma antagonist in adipocytes, enhanced PPRE reporter activation in normal mammary epithelia] cells while it had virtually no effect in any of the cancer cell lines tested. Within each cancer type, individual cell lines were found to respond differently to distinct PPAR gamma ligands. For instance, Ros, Cig, and PGJ2 were all potent agonist of PPAR gamma transactivation in lung adenocarcinorna cell lines while these same ligands had no effect in squamous cell or large cell carcinomas of the lung.Message levels of PPAR gamma and retinoid X receptor alpha (RXR alpha) in the individual cell lines were quantitated by real time-polymerase chain reaction (RT-PCR). The ratio of PPAR gamma to RXRa was predictive of how cells responded to co-treatment of Ros and 9-cis-retinoic acid, an RXR alpha agonist, in two out of three cell lines tested. These data indicate that PPAR gamma can be selectively modulated and suggests that it may be used as a therapeutic target for individual tumors. (c) 2005 Elsevier Ireland Ltd. All rights reserved.