Epigenetic modulation of the retinoid X receptor alpha by green tea in the azoxymethane-Apc Min/+ mouse model of intestinal cancer.
Epigenetic modulation of the retinoid X receptor alpha by green tea in the azoxymethane-Apc Min/+ mouse model of intestinal cancer.
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DOI：
10.1002/mc.20542
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发表时间：
2009-10
影响因子：
4.6
通讯作者：
Wargovich MJ
中科院分区：
文献类型：
--
作者：
Volate SR;Muga SJ;Issa AY;Nitcheva D;Smith T;Wargovich MJ
我们研究了绿茶（GT）抑制偶氮氧甲烷处理（AOM） ApcMin/+小鼠结直肠癌发生的可能机制。小鼠接受水或0.6% （w/v）的GT溶液作为唯一的饮料来源。GT治疗于8周龄开始，持续8周。治疗后新生肿瘤数量减少，差异有统计学意义（28%,P <0.05）。免疫组化分析显示，GT降低了β-catenin及其下游靶点cyclin D1的水平。为了探究其机制，我们进一步研究了视黄酸X受体α (RXRα)在AOM/ApcMin/+肿瘤中的表达。我们的研究结果表明，RXRα在AOM/ApcMin/+小鼠肠道肿瘤中选择性下调。其他视黄酸受体包括视黄酸受体α (RARα)、RARβ、RXRβ和RXRγ均在ApcMin/+腺瘤中表达。此外，我们的研究结果表明，RXRα下调是结直肠癌发生的早期事件，与β-catenin的表达无关。GT显著提高RXRα蛋白水平。此外，RT-PCR分析显示，GT诱导RXRα mRNA水平升高。对结肠DNA进行亚硫酸氢盐处理，然后对RXRα基因启动子区域的24个CpG位点进行焦磷酸测序，结果显示GT处理显著降低了CpG甲基化。结果表明，低浓度的GT足以抑制RXRα的沉默，抑制ApcMin/+小鼠肠道肿瘤的发生。
We investigated the possible mechanisms of inhibition of colorectal carcinogenesis by green tea (GT) in azoxymethane-treated (AOM) ApcMin/+ mice. Mice received water or a 0.6% (w/v) solution of GT as the only source of beverage. GT treatment commenced at the 8th week of age and lasted for 8 wk. The treatment caused a statistically significant reduction in the number of newly formed tumors (28%, P <0.05). Immunohistochemical analysis showed that GT decreased the levels of β-catenin and its downstream target cyclin D1. To probe a mechanism, we further investigated the expression of retinoic X receptor alpha (RXRα) in AOM/ApcMin/+ tumors. Our results show that RXRα is selectively downregulated in AOM/ApcMin/+ mouse intestinal tumors. In contrast, other retinoic receptors including retinoic acid receptor alpha (RARα), RARβ, RXRβ, and RXRγ were all expressed in ApcMin/+ adenomas. Furthermore, our results show that RXRα downregulation is an early event in colorectal carcinogenesis and is independent of β-catenin expression. GT significantly increased the protein levels of RXRα. In addition, RT-PCR analysis showed that GT induced a similar increase in the levels of RXRα mRNA. Genomic bisulfite treatment of colonic DNA followed by pyrosequencing of 24 CpG sites in the promoter region of RXRα gene showed a significant decrease in CpG methylation with GT treatment. The results suggest that a low concentration of GT is sufficient to desilence RXRα and inhibit intestinal tumorigenesis in the ApcMin/+ mouse.
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影响因子：
8.8
作者：
Jung, Y D;Kim, M S;Shin, B A;Chay, K O;Ahn, B W;Liu, W;Bucana, C D;Gallick, G E;Ellis, L M
通讯作者：
Ellis, L M
影响因子：
2.7
作者：
Colella, S;Shen, L;Krahe, R
通讯作者：
Krahe, R
影响因子：
--
作者：
BERRODIN, TJ;MARKS, MS;LAZAR, MA
通讯作者：
LAZAR, MA
影响因子：
3.6
作者：
Lee, WJ;Shim, JY;Zhu, BT
通讯作者：
Zhu, BT
影响因子：
4.8
作者：
Chung, JY;Park, JO;Yang, CS
通讯作者：
Yang, CS