Differentiation and reversal of malignant changes in colon cancer through PPARγ
Differentiation and reversal of malignant changes in colon cancer through PPARγ
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DOI：
10.1038/2030
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发表时间：
1998-09-01
期刊：
影响因子：
82.9
通讯作者：
Spiegelman, BM
中科院分区：
文献类型：
--
作者：
Sarraf, P;Mueller, E;Spiegelman, BM
PPAR γ是一种核受体，在脂肪谱系细胞的分化中具有主要的调节作用，最近被证明在结肠中表达。我们在这里表明，PPAR γ在分化良好和分化不良的腺癌、正常结肠黏膜和人结肠癌细胞系中都有高水平表达。在结肠癌细胞中，这种受体的配体激活导致线性和克隆生长的显著减少，癌胚抗原的表达增加，以及许多与结肠癌特异性相关的基因表达事件的逆转。当小鼠接受PPAR配体曲格列酮治疗时，源自人类结肠癌细胞的可移植肿瘤的生长明显减少。这些结果表明PPAR γ可以调节结肠癌细胞的生长和分化。
PPAR gamma is a nuclear receptor that has a dominant regulatory role in differentiation of cells of the adipose lineage, and has recently been shown to be expressed in the colon. We show here that PPAR gamma is expressed at high levels in both well- and poorly-differentiated adenocarcinomas, in normal colonic mucosa and in human colon cancer cell lines. Ligand activation of this receptor in colon cancer cells causes a considerable reduction in linear and clonogenic growth, increased expression of carcinoembryonic antigen and the reversal of many gene expression events specifically associated with colon cancer. Transplantable tumors derived from human colon cancer cells show a significant reduction of growth when mice are treated with troglitazone, a PPAR gamma ligand. These results indicate that the growth and differentiation of colon cancer cells can be modulated through PPAR gamma.