Krüppel-like Factor 5 Transcription Factor Promotes Microsomal Prostaglandin E2 Synthase 1 Gene Transcription in Breast Cancer

作者: Houjun Xia , Chunyan Wang , Wenlin Chen , Hailin Zhang , Leena Chaudhury

DOI: 10.1074/JBC.M113.483958

关键词:

摘要: The KLF5 (Kruppel-like factor 5) transcription is specifically expressed in a subset of estrogen receptor α-negative breast cancers. Although promotes cancer cell cycle progression, survival, and tumorigenesis, the mechanism by which still not entirely understood. Here, we demonstrate that mPGES1, encoding microsomal prostaglandin E2 synthase 1 (mPGES1), direct downstream target gene. overexpression or knockdown positively altered levels mPGES1 mRNA protein multiple lines. 12-O-Tetradecanoylphorbol-13-acetate induced expression both dosage- time-dependent manners. induction was essential for 12-O-tetradecanoylphorbol-13-acetate to induce expression. Additionally, bound gene proximal promoter activated its transcription. Both promoted production; regulated p21, p27, Survivin expression; likewise stimulated proliferation. Overexpression partially rescued knockdown-induced changes growth arrest MCF10A cells. Finally, correlated with α/progesterone receptor/HER2 triple-negative status. These findings suggest KLF5, making it new biomarker potential therapeutic

参考文章(56)
Masako Nakanishi, Vijay Gokhale, Emmanuelle J. Meuillet, Daniel W. Rosenberg, mPGES-1 as a target for cancer suppression: A comprehensive invited review "Phospholipase A2 and lipid mediators". Biochimie. ,vol. 92, pp. 660- 664 ,(2010) , 10.1016/J.BIOCHI.2010.02.006
Matthew C. Catley, Joanna E. Chivers, Lisa M. Cambridge, Neil Holden, Donna M. Slater, Karl J. Staples, Martin W. Bergmann, Peter Loser, Peter J. Barnes, Robert Newton, IL-1β-dependent activation of NF-κB mediates PGE2 release via the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase FEBS Letters. ,vol. 547, pp. 75- 79 ,(2003) , 10.1016/S0014-5793(03)00672-0
Nicholas W Bateman, Dongfeng Tan, Richard G Pestell, Jennifer D Black, Adrian R Black, None, Intestinal tumor progression is associated with altered function of KLF5. Journal of Biological Chemistry. ,vol. 279, pp. 12093- 12101 ,(2004) , 10.1074/JBC.M311532200
Florian Rörsch, Ivonne Wobst, Heiko Zettl, Manfred Schubert-Zsilavecz, Sabine Grösch, Gerd Geisslinger, Gisbert Schneider, Ewgenij Proschak, Nonacidic Inhibitors of Human Microsomal Prostaglandin Synthase 1 (mPGES 1) Identified by a Multistep Virtual Screening Protocol Journal of Medicinal Chemistry. ,vol. 53, pp. 911- 915 ,(2010) , 10.1021/JM9012505
Manuel D. Díaz-Muñoz, Inés C. Osma-García, Manuel Fresno, Miguel A. Iñiguez, Involvement of PGE2 and the cAMP signalling pathway in the up-regulation of COX-2 and mPGES-1 expression in LPS-activated macrophages. Biochemical Journal. ,vol. 443, pp. 451- 461 ,(2012) , 10.1042/BJ20111052
Ceshi Chen, Hina V. Bhalala, Robert L. Vessella, Jin-Tang Dong, KLF5 is frequently deleted and down‐regulated but rarely mutated in prostate cancer The Prostate. ,vol. 55, pp. 81- 88 ,(2003) , 10.1002/PROS.10205
Mandayam O Nandan, Hong S Yoon, Weidong Zhao, Lillian A Ouko, Sengthong Chanchevalap, Vincent W Yang, Krüppel-like factor 5 mediates the transforming activity of oncogenic H-Ras. Oncogene. ,vol. 23, pp. 3404- 3413 ,(2004) , 10.1038/SJ.ONC.1207397