title: PHD2 in tumour angiogenesis.
abstract: Originally identified as the enzymes responsible for catalysing the oxidation of specific, conserved proline residues within hypoxia-inducible factor-1alpha (HIF-1alpha), the additional roles for the prolyl hydroxylase domain (PHD) proteins have remained elusive. Of the four identified PHD enzymes, PHD2 is considered to be the key oxygen sensor, as knockdown of PHD2 results in elevated HIF protein. Several recent studies have highlighted the importance of PHD2 in tumourigenesis. However, there is conflicting evidence as to the exact role of PHD2 in tumour angiogenesis. The divergence seems to be because of the contribution of stromal-derived PHD2, and in particular the involvement of endothelial cells, vs tumour-derived PHD2. This review summarises our current understanding of PHD2 and tumour angiogenesis, focusing on the influences of PHD2 on vascular normalisation and neovascularisation.
authors.affiliation: Department of Radiation Oncology, University of California, 2340 Sutter Street, S-332, Box 1331, San Francisco, CA 94143-1331, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Chan
authors.forename: A J
authors.initials: AJ
authors.lastname: Giaccia
mesh_terms: D000818:Animals; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000209:etiology*; D011393:Procollagen-Proline Dioxygenase / Q000502:physiology*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases
references.citation: Cancer Cell. 2009 Jun 2;15(6):527-38
references.pmid: 19477431
references.citation: Genes Dev. 2001 Oct 15;15(20):2675-86
references.pmid: 11641274
references.citation: Cancer Cell. 2008 Dec 9;14(6):435-46
references.pmid: 19061835
references.citation: EMBO J. 1998 Jun 1;17(11):3005-15
references.pmid: 9606183
references.citation: Cancer Cell. 2008 Mar;13(3):206-20
references.pmid: 18328425
references.citation: EMBO J. 2003 Aug 15;22(16):4082-90
references.pmid: 12912907
references.citation: N Engl J Med. 2008 Dec 18;359(25):2685-92
references.pmid: 19092153
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9630-5
references.pmid: 11504942
references.citation: Mol Cancer Res. 2008 May;6(5):829-42
references.pmid: 18505927
references.citation: Trends Mol Med. 2002;8(4 Suppl):S62-7
references.pmid: 11927290
references.citation: J Cell Physiol. 2006 Nov;209(2):333-40
references.pmid: 16883594
references.citation: Cancer Res. 2000 Aug 1;60(15):4010-5
references.pmid: 10945599
references.citation: Urol Clin North Am. 1993 May;20(2):207-16
references.pmid: 8098558
references.citation: Nature. 1999 May 20;399(6733):271-5
references.pmid: 10353251
references.citation: Cancer Res. 2003 Dec 15;63(24):8777-83
references.pmid: 14695194
references.citation: Cancer Res. 1999 Nov 15;59(22):5830-5
references.pmid: 10582706
references.citation: Clin Cancer Res. 2008 Aug 1;14(15):4726-34
references.pmid: 18676741
references.citation: Int J Cancer. 2006 Mar 1;118(5):1144-53
references.pmid: 16161047
references.citation: Science. 2001 Apr 20;292(5516):464-8
references.pmid: 11292862
references.citation: Hypertension. 2007 Jan;49(1):178-84
references.pmid: 17101841
references.citation: Cancer Cell. 2005 Aug;8(2):131-41
references.pmid: 16098466
references.citation: Cancer Sci. 2009 Sep;100(9):1639-47
references.pmid: 19575748
references.citation: Cancer Res. 2006 Feb 1;66(3):1684-936
references.pmid: 16452228
references.citation: Genes Dev. 2002 Jun 15;16(12):1466-71
references.pmid: 12080085
references.citation: Mol Cell Biol. 2006 Nov;26(22):8336-46
references.pmid: 16966370
references.citation: Cancer Res. 2010 Jan 1;70(1):357-66
references.pmid: 20028863
references.citation: Cancer Cell. 2005 Aug;8(2):143-53
references.pmid: 16098467
references.citation: Nat Genet. 2008 Feb;40(2):170-80
references.pmid: 18176562
references.citation: Circulation. 2007 Aug 14;116(7):774-81
references.pmid: 17646578
references.citation: Annu Rev Pathol. 2007;2:145-73
references.pmid: 18039096
references.citation: Hum Mutat. 2010 Jan;31(1):41-51
references.pmid: 19802898
references.citation: Science. 2001 Apr 20;292(5516):468-72
references.pmid: 11292861
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18154-9
references.pmid: 17114296
references.citation: Science. 2002 Feb 1;295(5556):858-61
references.pmid: 11823643
references.citation: Cell. 2009 Mar 6;136(5):839-851
references.pmid: 19217150
references.citation: Nat Genet. 1994 May;7(1):85-90
references.pmid: 7915601
references.citation: Gastroenterology. 2010 Feb;138(2):606-15
references.pmid: 19786027
references.citation: Nature. 1998 Jul 30;394(6692):485-90
references.pmid: 9697772
references.citation: Cancer Cell. 2004 Nov;6(5):485-95
references.pmid: 15542432
references.citation: Cancer Res. 2007 Jan 15;67(2):563-72
references.pmid: 17234764
references.citation: Blood. 2008 Mar 15;111(6):3236-44
references.pmid: 18096761