Kruppel-like Factor 5 Transcription Factor Promotes Microsomal Prostaglandin E-2 Synthase 1 Gene Transcription in Breast Cancer

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	Kruppel-like Factor 5 Transcription Factor Promotes Microsomal Prostaglandin E-2 Synthase 1 Gene Transcription in Breast Cancer
	Xia HJ 1; Wang CY 1,2; Chen WL 4; Zhang HL 1; Chaudhury L 5; Zhou ZM 1; Liu R 1; Chen CS[*]1
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2013
卷号	288 期号:37 页码:26731-26740
通讯作者	chenc@mail.kiz.ac.cn
合作状况	其它
英文摘要	The KLF5 (Kruppel-like factor 5) transcription factor is specifically expressed in a subset of estrogen receptor alpha-negative breast cancers. Although KLF5 promotes breast cancer cell cycle progression, survival, and tumorigenesis, the mechanism by which KLF5 promotes breast cancer is still not entirely understood. Here, we demonstrate that mPGES1, encoding microsomal prostaglandin E-2 synthase 1 (mPGES1), is a KLF5 direct downstream target gene. KLF5 overexpression or knockdown positively altered the levels of mPGES1 mRNA and protein in multiple breast cell lines. 12-O-Tetradecanoylphorbol-13-acetate induced the expression of both KLF5 and mPGES1 in dosage- and time-dependent manners. The induction of KLF5 was essential for 12-O-tetradecanoylphorbol-13-acetate to induce mPGES1 expression. Additionally, KLF5 bound to the mPGES1 gene proximal promoter and activated its transcription. Both KLF5 and mPGES1 promoted prostaglandin E-2 production; regulated p21, p27, and Survivin downstream gene expression; and likewise stimulated cell proliferation. Overexpression of mPGES1 partially rescued the KLF5 knockdown-induced downstream gene expression changes and growth arrest in MCF10A cells. Finally, we demonstrate that the expression of mPGES1 was positively correlated with the estrogen receptor alpha/progesterone receptor/HER2 triple-negative status. These findings suggest that mPGES1 is a target gene of KLF5, making it a new biomarker and a potential therapeutic target for triple-negative breast cancers.
收录类别	SCI
资助信息	This work was supported by Stem Cell and Regenerative Medicine Research Grant XDA01040406 from the Strategic Priority Research Program of the Chinese Academy of Sciences; National Natural Science Foundation of China Grants 81202110, 81272930, and U1132605; Grant 2010CI114 from the Top Talents Program of Yunnan Province, China; Grant 2012FB185 from the Science and Technological Key Project of Yunnan Province (to R. L.); and the “Western Light” Talents Training Program of the Chinese Academy of Sciences (to H. X.).
语种	英语
WOS记录号	WOS:000330594500038
公开日期	2014-10-22
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/152453/8127]
专题	昆明动物研究所_肿瘤生物学昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	1.Key Laboratory of Animal Models and Human Disease MechanismsofChineseAcademyofSciencesandYunnan Province,KunmingInstituteofZoology,ChineseAcademyofSciences,Kunming,Yunnan650223,China 2.University of the ChineseAcademyofSciences,Beijing100039,China 3.DepartmentofPathology,FirstAffiliatedHospitalofKunmingMedical University 4.CancerHospital,KunmingMedicalUniversity,Kunming,Yunnan650031,China 5.CenterforCellBiology andCancerResearch,AlbanyMedicalCollege,Albany, New York 12208
推荐引用方式 GB/T 7714	Xia HJ,Wang CY,Chen WL,et al. Kruppel-like Factor 5 Transcription Factor Promotes Microsomal Prostaglandin E-2 Synthase 1 Gene Transcription in Breast Cancer[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2013,288(37):26731-26740.
APA	Xia HJ.,Wang CY.,Chen WL.,Zhang HL.,Chaudhury L.,...&Chen CS[*].(2013).Kruppel-like Factor 5 Transcription Factor Promotes Microsomal Prostaglandin E-2 Synthase 1 Gene Transcription in Breast Cancer.JOURNAL OF BIOLOGICAL CHEMISTRY,288(37),26731-26740.
MLA	Xia HJ,et al."Kruppel-like Factor 5 Transcription Factor Promotes Microsomal Prostaglandin E-2 Synthase 1 Gene Transcription in Breast Cancer".JOURNAL OF BIOLOGICAL CHEMISTRY 288.37(2013):26731-26740.