过氧化物酶体增殖物激活受体γ诱导人结肠癌细胞的生长停滞和分化标志物。
Peroxisome proliferator-activated receptor gamma induces growth arrest and differentiation markers of human colon cancer cells.
作者信息
Kitamura S, Miyazaki Y, Shinomura Y, Kondo S, Kanayama S, Matsuzawa Y
机构信息
Second Department of Internal Medicine, Osaka University Medical School.
出版信息
Jpn J Cancer Res. 1999 Jan;90(1):75-80. doi: 10.1111/j.1349-7006.1999.tb00668.x.
Abstract
Peroxisome proliferator-activated receptor gamma (PPAR gamma), one of the nuclear receptors expressed in adipose tissue, plays an important role in adipocyte differentiation. In this study, we investigated the expression of PPAR gamma and its role in cellular growth and differentiation in six colon cancer cell lines: HT-29, CaCo-2, SW-480, DLD-1, LoVo, and T-84. All six expressed PPAR gamma mRNA and protein, shown respectively on northern and western blot analyses. Luciferase assay in HT-29 cells, which strongly express PPAR gamma, showed that troglitazone, a selective ligand for PPAR gamma, transactivated the transcription of a peroxisome proliferator response element (PPRE)-driven promoter. Furthermore, troglitazone caused a marked decrease in [3H]thymidine incorporation and G1 cell-cycle arrest determined by flow cytometry. Finally, troglitazone induced expression of mRNAs for villin and intestinal alkaline phosphatase, markers for enterocyte differentiation. In conclusion, human colon cancer cells express PPAR gamma, the ligands of which inhibit cell growth and induce differentiation markers.
摘要
过氧化物酶体增殖物激活受体γ（PPARγ）是在脂肪组织中表达的核受体之一，在脂肪细胞分化中起重要作用。在本研究中，我们调查了PPARγ在六种结肠癌细胞系（HT-29、CaCo-2、SW-480、DLD-1、LoVo和T-84）中的表达及其在细胞生长和分化中的作用。通过Northern印迹和Western印迹分析分别显示，所有这六种细胞系均表达PPARγ mRNA和蛋白。在强烈表达PPARγ的HT-29细胞中进行的荧光素酶测定表明，PPARγ的选择性配体曲格列酮可反式激活过氧化物酶体增殖物反应元件（PPRE）驱动的启动子的转录。此外，曲格列酮导致[3H]胸苷掺入显著减少，并通过流式细胞术确定G1期细胞周期停滞。最后，曲格列酮诱导了绒毛蛋白和肠碱性磷酸酶的mRNA表达，这两种蛋白是肠上皮细胞分化的标志物。总之，人结肠癌细胞表达PPARγ，其配体可抑制细胞生长并诱导分化标志物。
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