Sarraf P, Mueller E, Jones D, King F J, DeAngelo D J, Partridge J B, Holden S A, Chen L B, Singer S, Fletcher C, Spiegelman B M
Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nat Med. 1998 Sep;4(9):1046-52. doi: 10.1038/2030.
PPARgamma 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 PPARgamma 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 PPARgamma ligand. These results indicate that the growth and differentiation of colon cancer cells can be modulated through PPARgamma.
过氧化物酶体增殖物激活受体γ（PPARγ）是一种核受体，在脂肪谱系细胞的分化中起主要调节作用，最近已证明其在结肠中表达。我们在此表明，PPARγ在高分化和低分化腺癌、正常结肠黏膜及人结肠癌细胞系中均高表达。该受体在结肠癌细胞中的配体激活导致线性生长和克隆形成生长显著降低，癌胚抗原表达增加，并逆转了许多与结肠癌特异性相关的基因表达事件。当用PPARγ配体曲格列酮处理小鼠时，源自人结肠癌细胞的可移植肿瘤生长显著降低。这些结果表明，结肠癌细胞的生长和分化可通过PPARγ进行调节。
