title: Kruppel-like factor 5 transcription factor promotes microsomal prostaglandin E2 synthase 1 gene transcription in breast cancer.
abstract: The KLF5 (Krüppel-like factor 5) transcription factor is specifically expressed in a subset of estrogen receptor α-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 E2 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 E2 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 α/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.
authors.affiliation: From the Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors.forename: Houjun
authors.initials: H
authors.lastname: Xia
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.forename: Wenlin
authors.initials: W
authors.lastname: Chen
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
authors.forename: Leena
authors.initials: L
authors.lastname: Chaudhury
authors.forename: Zhongmei
authors.initials: Z
authors.lastname: Zhou
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Ceshi
authors.initials: C
authors.lastname: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D047369:Chromatin Immunoprecipitation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D061986:MCF-7 Cells; D008861:Microsomes / Q000378:metabolism; D010703:Phorbol Esters / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D000077022:Survivin; D014158:Transcription, Genetic
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D010703:Phorbol Esters; D000077022:Survivin; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases
keywords: Biomarkers; Breast Cancer; KLF5; PGE2; Phorbol Esters; Proliferation; Transcription; mPGES1
references.citation: Biochim Biophys Acta. 2003 Jun 19;1627(2-3):79-84
references.pmid: 12818425
references.citation: J Immunol. 2002 Jun 1;168(11):5811-6
references.pmid: 12023384
references.citation: Oncogene. 2007 Jan 18;26(3):456-61
references.pmid: 16832343
references.citation: J Lipid Res. 2005 Dec;46(12):2636-48
references.pmid: 16204198
references.citation: J Biol Chem. 2004 Mar 26;279(13):12093-101
references.pmid: 14726538
references.citation: Circ Res. 1999 Oct 29;85(9):787-95
references.pmid: 10532946
references.citation: Biochimie. 2010 Jun;92(6):660-4
references.pmid: 20159031
references.citation: Surgery. 2006 Aug;140(2):289-96
references.pmid: 16904982
references.citation: Breast Cancer Res Treat. 2012 Feb;132(1):51-9
references.pmid: 21533532
references.citation: Int J Cancer. 2006 Mar 15;118(6):1346-55
references.pmid: 16184550
references.citation: J Pathol. 2006 Feb;208(3):356-63
references.pmid: 16353170
references.citation: Mol Endocrinol. 2011 Jul;25(7):1137-44
references.pmid: 21566082
references.citation: Oncogene. 2012 Feb 16;31(7):842-57
references.pmid: 21743491
references.citation: J Biol Chem. 2009 Jun 19;284(25):16791-16798
references.pmid: 19411256
references.citation: Oncogene. 2012 Jul 19;31(29):3457-66
references.pmid: 22081067
references.citation: Eur J Pharmacol. 2009 Oct 12;620(1-3):112-9
references.pmid: 19686718
references.citation: Cancer Lett. 2003 Dec 30;202(2):131-6
references.pmid: 14643442
references.citation: Cancer Res. 2005 Jun 1;65(11):4496-9
references.pmid: 15930264
references.citation: J Biol Chem. 2002 Aug 9;277(32):28601-8
references.pmid: 12034740
references.citation: J Pharmacol Exp Ther. 2010 Mar;332(3):840-8
references.pmid: 19934399
references.citation: J Reprod Immunol. 2010 Jan;84(1):66-74
references.pmid: 19945173
references.citation: Int J Cancer. 2007 Jul 1;121(1):80-87
references.pmid: 17330240
references.citation: J Biochem. 2009 Nov;146(5):683-91
references.pmid: 19628677
references.citation: Carcinogenesis. 2012 Jan;33(1):59-67
references.pmid: 22045023
references.citation: Pathol Oncol Res. 2012 Apr;18(2):161-8
references.pmid: 21674249
references.citation: J Immunol. 2001 Jul 1;167(1):469-74
references.pmid: 11418684
references.citation: Clin Cancer Res. 2006 Apr 15;12(8):2442-8
references.pmid: 16638850
references.citation: J Biol Chem. 2000 Oct 20;275(42):32783-92
references.pmid: 10869354
references.citation: Oncogene. 2004 Apr 22;23(19):3404-13
references.pmid: 15077182
references.citation: J Biol Chem. 2003 May 23;278(21):19396-405
references.pmid: 12626523
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Jun;292(6):G1784-92
references.pmid: 17395897
references.citation: Prostate. 2003 May 1;55(2):81-8
references.pmid: 12661032
references.citation: Gut. 2012 May;61(5):673-84
references.pmid: 22315472
references.citation: Biochem J. 2012 Apr 15;443(2):451-61
references.pmid: 22268508
references.citation: J Biol Chem. 2006 May 26;281(21):14711-8
references.pmid: 16595680
references.citation: Biochem Pharmacol. 2010 Nov 1;80(9):1365-72
references.pmid: 20688046
references.citation: Nucleic Acids Res. 2006 Feb 25;34(4):1216-23
references.pmid: 16500892
references.citation: J Biol Chem. 2007 May 25;282(21):15541-9
references.pmid: 17430902
references.citation: J Cell Biochem. 2012 Dec;113(12):3653-62
references.pmid: 22740037
references.citation: Eur J Cell Biol. 2002 Jun;81(6):323-34
references.pmid: 12113473
references.citation: FEBS Lett. 2003 Jul 17;547(1-3):75-9
references.pmid: 12860389
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18757-62
references.pmid: 19846775
references.citation: Oncogene. 2009 Oct 22;28(42):3702-13
references.pmid: 19668233
references.citation: Oncogene. 2005 May 5;24(20):3319-27
references.pmid: 15735697
references.citation: Cell Mol Life Sci. 2009 Aug;66(16):2691-706
references.pmid: 19448973
references.citation: FEBS Lett. 2000 Apr 7;471(1):78-82
references.pmid: 10760517
references.citation: Nat Med. 2002 Aug;8(8):856-63
references.pmid: 12101409
references.citation: Biochem J. 2012 Apr 15;443(2):561-71
references.pmid: 22260630
references.citation: J Med Chem. 2010 Jan 28;53(2):911-5
references.pmid: 20025212
references.citation: Cancer Res. 2008 May 1;68(9):3251-9
references.pmid: 18451151
references.citation: Nat Rev Cancer. 2010 Mar;10(3):181-93
references.pmid: 20168319
references.citation: Nature. 2002 Sep 26;419(6905):407-11
references.pmid: 12353038
references.citation: Cancer Res. 2000 Apr 15;60(8):2101-3
references.pmid: 10786667
references.citation: Endocr Relat Cancer. 2012 Nov 06;19(6):741-50
references.pmid: 22936544
references.citation: Pharmacol Rev. 2007 Sep;59(3):207-24
references.pmid: 17878511
references.citation: Cell Metab. 2005 Jan;1(1):27-39
references.pmid: 16054042