PPARdelta is pro-tumorigenic in a mouse model of COX-2-induced mammary cancer.
PPARdelta is pro-tumorigenic in a mouse model of COX-2-induced mammary cancer.
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DOI：
10.1016/j.prostaglandins.2008.11.004
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发表时间：
2009-04
影响因子：
2.9
通讯作者：
Hla T
中科院分区：
文献类型：
--
作者：
Ghosh M;Ai Y;Narko K;Wang Z;Peters JM;Hla T
环氧合酶-2（考克斯-2）在炎症和癌症中过表达，通过产生具有生物活性的前列腺素调节血管生成和肿瘤发生。以前，我们发现考克斯-2在转基因小鼠乳腺中的过表达诱导了血管生成开关，并将乳腺上皮转化为浸润性乳腺癌。由于考克斯-2衍生的前列腺素类物质可以激活核受体PPARδ，我们在FVB/N背景下将Pparδ−/−小鼠与考克斯-2转基因小鼠杂交。PPARδ在未孕、妊娠和哺乳期小鼠乳腺中均呈组成性表达。与野生型小鼠相比，Pparδ−/−小鼠中考克斯-2转基因小鼠的乳腺增生和肿瘤发生显著减少。对乳腺组织的分析表明，免疫反应性Ki-67、细胞周期蛋白D1和磷酸化组蛋白3（Phospho H3）在Pparδ−/−小鼠中减少，表明PPARδ激活调节乳腺细胞增殖。我们推测，核受体过氧化物酶体增殖物激活受体δ的考克斯-2衍生的前列腺素可能参与乳腺上皮细胞的增殖，因此有助于乳腺癌的发展。
Cyclooxygenase-2 (COX-2), overexpressed in inflammatory conditions and cancer, regulates angiogenesis and tumorigenesis via the production of biologically active prostanoids. Previously, we showed that COX-2 over-expression in the mammary gland of transgenic mice induces an angiogenic switch and transforms the mammary epithelium into invasive mammary carcinoma. Since COX-2-derived prostanoids can activate the nuclear receptor PPARδ, we crossed Pparδ−/− mice with COX-2 transgenic mice in the FVB/N background. PPARδ was expressed constitutively in the mammary gland of virgin, pregnant and lactating mice. Mammary hyperplasia and tumorigenesis in the COX-2 transgenic mice was markedly reduced in the Pparδ−/− mice compared to their wild type counterparts. Analysis of the mammary tissues indicated that immunoreactive Ki-67, cyclin D1 and phosphorylated histone 3 (Phospho H3) were reduced in Pparδ−/− mice, suggesting that PPARδ activation regulates cell proliferation in the mammary gland. We postulate that activation of the nuclear receptor PPARδ by COX-2-derived prostanoids may be involved in the proliferation of mammary epithelial cells and therefore contribute to mammary cancer development.
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DOI：
10.1186/bcr1678
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Howe LR
通讯作者：
Howe LR
影响因子：
4.8
作者：
Kim, DJ;Akiyama, TE;Peters, JM
通讯作者：
Peters, JM
影响因子：
8
作者：
Reed, KR;Sansom, OJ;Clarke, AR
通讯作者：
Clarke, AR
影响因子：
5.4
作者：
Hollowood, Timothy;Kumar, S. Prem;Naqvi, Asad
通讯作者：
Naqvi, Asad
影响因子：
10.5
作者：
Lim, H;Gupta, RA;Dey, SK
通讯作者：
Dey, SK