Stem cell antigen-1 deficiency enhances the chemopreventive effect of peroxisome proliferator-activated receptorγ activation.
Stem cell antigen-1 deficiency enhances the chemopreventive effect of peroxisome proliferator-activated receptorγ activation.
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干细胞抗原1 缺乏增强了过氧化物酶体增殖物激活受体γ 激活的化学预防作用。
DOI：
10.1158/1940-6207.capr-11-0256
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Glazer,RobertI
中科院分区：
文献类型：
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作者：
Yuan,Hongyan;Upadhyay,Geeta;Yin,Yuzhi;Kopelovich,Levy;Glazer,RobertI
干细胞抗原-1（Sca-1，Ly 6A）是一种甘油磷脂酰肌醇（GPI）锚定蛋白，被鉴定为骨髓干细胞的鼠标志物。尽管Sca-1被广泛用于富集各种组织中的干细胞和祖细胞，但对其在正常和恶性细胞中的功能和相关信号通路知之甚少。在此，我们报告了乳腺中Sca-1的缺失导致了PPARγ和PTEN的水平升高，以及pSer 84 PPAR γ、pERK 1/2和PPARδ的降低。这种表型与Sca-1敲除小鼠对PPARγ激动剂GW 7845的敏感性显著增加和对PPARδ激动剂GW 501516的不敏感性相关。通过RNA干扰减少乳腺肿瘤细胞中Sca-1的表达，导致与Sca-1缺陷型乳腺相似的表型，这通过增加的PPARγ表达和转录活性得到证明，部分原因是对蛋白酶体降解的敏感性降低。这些数据表明Sca-1是PPARγ的肿瘤抑制作用的负调节因子。Cancer Prev Res; 5（1）; 51-60。©2011 AACR。
Stem cell antigen-1 (Sca-1, Ly6A) is a glycerophosphatidylinositol (GPI)-anchored protein that was identified as a murine marker of bone marrow stem cells. Although Sca-1 is widely used to enrich for stem and progenitor cells in various tissues, little is known about its function and associated signaling pathways in normal and malignant cells. Here, we report that the absence of Sca-1 in the mammary gland resulted in higher levels of PPARγ and PTEN, and a reduction of pSer84PPARγ, pERK1/2, and PPARδ. This phenotype correlated with markedly increased sensitivity of Sca-1 null mice to PPARγ agonist GW7845 and insensitivity to PPARδ agonist GW501516. Reduction of Sca-1 expression in mammary tumor cells by RNA interference resulted in a phenotype similar to the Sca-1 deficient mammary gland, as evidenced by increased PPARγ expression and transcriptional activity, resulting in part from a lesser susceptibility to proteasomal degradation. These data implicate Sca-1 as a negative regulator of the tumor suppressor effects of PPARγ.Cancer Prev Res; 5(1); 51–60. ©2011 AACR.