期刊
EXPERIMENTAL CELL RESEARCH
卷 313, 期 16, 页码 3486-3496出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2007.06.028
关键词
15-deoxy-Delta(12,14)-prostaglandin J(2); cancer cells; apoptosis; human telomerase; reverse transcriptase; ER beta; mitogen-activated protein kinase
The nuclearhormone receptor peroxisome proliferator-activated receptor (PPAR)-gamma plays a role in cancer development in addition to its role in glucose metabolism. The natural ligand of PPAR-gamma, namely, 15-deoxy-Delta(12,14) -prostaglandin J(2) (15d-PGJ(2)), has been shown to possess antineoplastic activity in cancer cells. However, the mechanism underlying its antineoplastic activity remains to be elucidated. Inhibition of the expression of human telomerase reverse transcriptase (hTERT), a major determinant of telomerase activity, reportedly induces rapid apoptosis in cancer cells. In this study, we investigated the effect of 15d-PGJ(2) on hTERT expression. We found that 15d-PGJ(2) induced apoptosis in the MIAPaCa-2 pancreatic cancer cells and dose-dependently decreased hTERT mRNA and protein expression. Down-regulation of hTERT expression by hTERT-specific small inhibitory RNA also induced apoptosis. Furthermore, 15d-PGJ(2) attenuated the DNA binding of estrogen receptor (ER). MIAPaCa-2 expressed only ER beta, and although its expression did not decrease due to 15d-PGJ(2), its phosphorylation was suppressed. Additionally, a mitogen-activated protein kinase (MAPK) kinase inhibitor decreased ER phosphorylation, and 15d-PGJ(2) attenuated MAPK activity. We conclude that hTERT down-regulation by 15d-PGJ(2) plays an important role in the proapoptotic property of the latter. Furthermore, 15d-PGJ(2) inhibits ER beta-mediated hTERT gene transcription by suppressing ER beta phosphorylation via the inhibition of MAP kinase signaling. (c) 2007 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据