A truncated human Ah receptor suppresses growth of human cervical tumor xenografts by interfering with hypoxia signaling.
We used a xenograft model to investigate whether the aryl hydrocarbon receptor deletion construct CDelta553 suppresses tumor growth. HeLa cells that were infected with CDelta553 expressing adenovirus (Ad553) formed very small tumors whereas the control adenovirus-infected cells formed large tumors at day 15. CDelta553 inhibited the formation of the HIF-1 DNA complex and suppressed the induction of the HIF-1alpha target proteins CAIX and GLUT1. The Ad553 tumors had less HIF-1 function since they showed reduced microvessel formation and lesser amounts of HIF-1alpha, Arnt, phospho-Akt, CAIX, and GLUT1. Proteasome-mediated Arnt degradation was enhanced in Ad553-infected HeLa cells and tumors.
Wang
Depeng
D
Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, United States.
Faridi
Jesika S
JS
Li
Yanjie
Y
Chan
William K
WK
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy*; D050505:Mutant Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D015202:Protein Engineering / Q000379:methods; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D017384:Sequence Deletion; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
C497396:ARNT protein, human; D050505:Mutant Proteins; D018336:Receptors, Aryl Hydrocarbon; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator
Mol Pharm. 2006 Nov-Dec;3(6):695-703
17140257
Cancer Cell. 2005 Aug;8(2):99-110
16098463
J Biol Chem. 1995 Jan 20;270(3):1230-7
7836384
FEBS Lett. 2000 Feb 18;468(1):53-8
10683440
Mol Pharmacol. 1999 Dec;56(6):1127-37
10570039
Cell Death Differ. 2008 Apr;15(4):678-85
18259193
Cancer Res. 2002 May 1;62(9):2493-7
11980639
Cancer Res. 2000 Mar 15;60(6):1541-5
10749120
Mol Cell Biol. 1996 Sep;16(9):4604-13
8756616
Anticancer Res. 2000 May-Jun;20(3A):1527-33
10928066
J Biol Chem. 2004 Apr 2;279(14):13506-13
14726529
Ann N Y Acad Sci. 1993 Jun 23;685:624-40
8395783
J Biol Chem. 2009 Sep 11;284(37):25135-48
19617630
Mol Cell Biol. 2001 Jun;21(12):3995-4004
11359907
Clin Cancer Res. 2002 Jun;8(6):1831-7
12060624
Trends Cell Biol. 2008 Apr;18(4):165-73
18296052
Int J Cancer. 2009 Feb 15;124(4):763-71
19030186
J Biol Chem. 2005 Aug 5;280(31):28731-41
15946950
J Cell Sci. 2001 Nov;114(Pt 22):4051-61
11739637
Cancer Res. 2008 Oct 15;68(20):8635-42
18922940
Nat Med. 2000 Dec;6(12):1335-40
11100117
Cancer Res. 2000 Sep 1;60(17):4693-6
10987269
J Biol Chem. 1999 Nov 12;274(46):32631-7
10551817
J Biol Chem. 1999 Apr 23;274(17):12115-23
10207038