title: Involvement of estrogen receptor β5 in the progression of glioma.
abstract: Emerging evidence suggests a decline of ERβ expression in various peripheral cancers. ERβ has been proposed as a cancer brake that inhibits tumor proliferation. In the current study, we have identified ERβ5 as the predominant isoform of ERβ in human glioma and its expression was significantly increased in human glioma as compared with non-neoplastic brain tissue. Hypoxia and activation of hypoxia inducible factor (HIF) increased ERβ transcription in U87 cells, suggesting elevated ERβ expression in glioma might be induced by the hypoxic stress in the tumor. Over-expression of either ERβ1 or ERβ5 increased PTEN expression and inhibited activation of the PI3K/AKT/mTOR pathway. In addition, ERβ5 inhibited the MAPK/ERK pathway. In U87 cells, ERβ1 and ERβ5 inhibit cell proliferation and reduced cells in the S+G2/M phase. Our findings suggest hypoxia induced ERβ5 expression in glioma as a self-protective mechanism against tumor proliferation and that ERβ5 might serve as a therapeutic target for the treatment of glioma.
authors: Department of Pharmacology and Neuroscience, Institute for Alzheimer's Disease and Aging Research, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors: Wenjun
authors: W
authors: Li
authors: Ali
authors: A
authors: Winters
authors: Ethan
authors: E
authors: Poteet
authors: Myoung-Gwi
authors: MG
authors: Ryou
authors: Song
authors: S
authors: Lin
authors: Shuyu
authors: S
authors: Hao
authors: Zhen
authors: Z
authors: Wu
authors: Fang
authors: F
authors: Yuan
authors: Kimmo J
authors: KJ
authors: Hatanpaa
authors: James W
authors: JW
authors: Simpkins
authors: Shao-Hua
authors: SH
authors: Yang
mesh_terms: D000704:Analysis of Variance; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D047629:Estrogen Receptor beta / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D010101:Oxygen Consumption / Q000502:physiology; D012333:RNA, Messenger; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D047629:Estrogen Receptor beta; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger
references: J Clin Oncol. 1999 May;17(5):1474-81
references: 10334533
references: Brain Res. 2011 Apr 28;1387:141-8
references: 21376707
references: Semin Reprod Med. 2012 Jan;30(1):5-13
references: 22271289
references: Endocr Relat Cancer. 2004 Sep;11(3):537-51
references: 15369453
references: Oncogene. 2003 Aug 7;22(32):5011-20
references: 12902984
references: Clin Cancer Res. 2004 Sep 1;10(17):5769-76
references: 15355905
references: J Cereb Blood Flow Metab. 2005 Apr;25(4):427-30
references: 15689954
references: Clin Cancer Res. 1996 Apr;2(4):619-22
references: 9816211
references: Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):739-42
references: 21353747
references: Endocrinology. 2001 Sep;142(9):4120-30
references: 11517191
references: Adv Exp Med Biol. 1994;345:465-70
references: 8079745
references: Cancer Res. 1997 Oct 1;57(19):4183-6
references: 9331071
references: J Biol Chem. 2002 Jul 5;277(27):24353-60
references: 11986316
references: Endocrine. 2005 Aug;27(3):227-38
references: 16230778
references: Endocr Relat Cancer. 2010 Jun 25;17(3):675-89
references: 20501637
references: J Neurochem. 2011 Jul;118(1):93-104
references: 21281310
references: Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1566-71
references: 14745018
references: J Biol Chem. 2005 Jun 3;280(22):21491-7
references: 15790569
references: Endocrinology. 2009 Mar;150(3):1112-21
references: 19008315
references: J Neurooncol. 2006 Mar;77(1):17-23
references: 16292491
references: Cancer Res. 2004 Jan 1;64(1):423-8
references: 14729654
references: Nucleic Acids Res. 2009 May;37(8):2584-95
references: 19264808
references: Breast Cancer Res. 2011 Apr 14;13(2):R43
references: 21492444
references: Endocrinology. 1999 Dec;140(12):5566-78
references: 10579320
references: Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13162-7
references: 16938840
references: Endocr Relat Cancer. 2005 Dec;12(4):903-16
references: 16322330
references: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12479-84
references: 9356475
references: Cancer Res. 2004 Mar 1;64(5):1886-92
references: 14996753
references: J Clin Oncol. 2008 Aug 1;26(22):3727-34
references: 18669459
references: Endocrinology. 2011 Dec;152(12):4537-49
references: 21990315
references: Cancer Res. 1999 Mar 15;59(6):1175-9
references: 10096542
references: Breast Cancer Res. 2011 Mar 10;13(2):R27
references: 21392396
references: Lung Cancer. 2008 Jan;59(1):88-94
references: 17905466
references: Biochem Biophys Res Commun. 1998 Jun 9;247(1):75-8
references: 9636657
references: Mol Cancer Ther. 2012 May;11(5):1174-82
references: 22442308
references: J Steroid Biochem Mol Biol. 2001 Jul;78(1):33-40
references: 11530282
references: Clin Cancer Res. 2004 Nov 15;10(22):7490-9
references: 15569979
references: Cell Cycle. 2012 Aug 1;11(15):2911-21
references: 22810004
references: Cancer Sci. 2008 Dec;99(12):2365-72
references: 19032364
references: Biochem Biophys Res Commun. 2000 Aug 28;275(2):682-9
references: 10964723
references: Cell. 2012 Mar 30;149(1):49-62
references: 22401813
references: Breast Cancer Res. 2011 Mar 24;13(2):R32
references: 21435239
references: Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2714-20
references: 18281611
references: J Mol Endocrinol. 2004 Dec;33(3):773-82
references: 15591034
references: Clin Cancer Res. 2008 Aug 15;14(16):5228-35
references: 18698041
references: Cancer Res. 2009 Aug 1;69(15):6100-6
references: 19602591
references: Arch Toxicol. 2012 Oct;86(10):1491-504
references: 22648069
references: Oncogene. 2003 Oct 23;22(48):7600-6
references: 14576822
references: Cancer. 2001 Oct 15;92(8):2076-83
references: 11596023
references: Am J Pathol. 2000 Jan;156(1):29-35
references: 10623650