5 '-AMP-activated protein kinase (AMPK) regulates progesterone receptor transcriptional activity in breast cancer cells

doi:10.1016/j.bbrc.2011.11.018

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	5 '-AMP-activated protein kinase (AMPK) regulates progesterone receptor transcriptional activity in breast cancer cells
	Wu, Li 2; Huang, Xiao-jie 2; Yang, Cheng-hong 2; Deng, Si-si 1; Qian, Min 2; Zang, Yi1 ; Li, Jia1,2
刊名	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
	2011-12-09
卷号	416 期号:1-2 页码:172-177
关键词	Progesterone receptor AMPK AICAR Metformin Compound C
ISSN号	0006-291X
DOI	10.1016/j.bbrc.2011.11.018
文献子类	Article
英文摘要	The steroid hormone progesterone is an essential regulator of the cellular processes that are required for the development and maintenance of reproductive function. The diverse effects of progesterone are mediated by the progesterone receptor (PR). The functions of the PR are regulated not only by ligands but also by modulators of various cell signaling pathways. However, it is not clear which energy state regulates PR activity. AMP-activated protein kinase (AMPK), a serine/threonine protein kinase, is a key modulator of energy homeostasis. Once activated by an increasing cellular AMP:ATP ratio, AMPK switches off ATP-consuming processes and switches on ATP-producing processes. We found that both 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR) and metformin, traditional pharmacological activators of AMPK, inhibited the PR pathway, as evidenced by progesterone response element (PRE)-driven luciferase activity and PR target gene expression. Compound C, an inhibitor of AMPK, partly but significantly reversed the anti-PR effects of AICAR and metformin. The downregulation of endogenous AMPK by small interfering RNAs (siRNAs) stimulated PR activity. AMPK activation by AICAR decreased the progesterone-induced phosphorylation of PR at serine 294 and inhibited the recruitment of PR to an endogenous PRE. Taken together, our data suggest that AMPK, an energy sensor, is involved in the regulation of PR signaling. (C) 2011 Elsevier Inc. All rights reserved.
资助项目	National Natural Science Foundation of China[81125023] ; National Science and Technology Major Project[2007CB914201] ; National Science and Technology Major Project[2009CB940900] ; Chinese Academy of Science[XDA01040303] ; Chinese Academy of Science[KSCX2-EW-R-15]
WOS关键词	GRANULOSA-CELLS ; PHOSPHORYLATION ; RESTRICTION ; SECRETION ; METFORMIN ; ENERGY ; CREB
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000298222100029
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278305]
专题	国家新药筛选中心
通讯作者	Zang, Yi
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 2.E China Normal Univ, Sch Life Sci, Shanghai 200062, Peoples R China;
推荐引用方式 GB/T 7714	Wu, Li,Huang, Xiao-jie,Yang, Cheng-hong,et al. 5 '-AMP-activated protein kinase (AMPK) regulates progesterone receptor transcriptional activity in breast cancer cells[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2011,416(1-2):172-177.
APA	Wu, Li.,Huang, Xiao-jie.,Yang, Cheng-hong.,Deng, Si-si.,Qian, Min.,...&Li, Jia.(2011).5 '-AMP-activated protein kinase (AMPK) regulates progesterone receptor transcriptional activity in breast cancer cells.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,416(1-2),172-177.
MLA	Wu, Li,et al."5 '-AMP-activated protein kinase (AMPK) regulates progesterone receptor transcriptional activity in breast cancer cells".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 416.1-2(2011):172-177.