PMID- 20978507
OWN - NLM
STAT- MEDLINE
DCOM- 20110301
LR  - 20220321
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 103
IP  - 10
DP  - 2010 Nov 9
TI  - PHD3 regulates differentiation, tumour growth and angiogenesis in pancreatic 
      cancer.
PG  - 1571-9
LID - 10.1038/sj.bjc.6605936 [doi]
AB  - PURPOSE: Tumour hypoxia activates hypoxia-inducible factor-1 (HIF-1) and 
      indluences angiogenesis, cell survival and invasion. Prolyl hydroxylase-3 (PHD3) 
      regulates degradation of HIF-1alpha. The effects of PHD3 in tumour growth are largely 
      unknown. EXPERIMENTAL DESIGN: PHD3 expression was analysed in human pancreatic 
      cancer tissues and cancer cell lines by real-time quantitative PCR and 
      immunohistochemistry. PHD3 overexpression was established by stable transfection 
      and downregulation by short interfering RNA technology. VEGF was quantified by 
      enzyme-linked immunosorbent assay. Matrigel invasion assays were performed to 
      examine tumour cell invasion. Apoptosis was measured by annexin-V staining and 
      caspase-3 assays. The effect of PHD3 on tumour growth in vivo was evaluated in an 
      established orthotopic murine model. RESULTS: PHD3 was upregulated in 
      well-differentiated human tumours and cell lines, and regulated hypoxic VEGF 
      secretion. PHD3 overexpression mediated tumour cell growth and invasion by 
      induction of apoptosis in a nerve growth factor-dependent manner by the 
      activation of caspase-3 and phosphorylation of focal adhesion kinase HIF-1 
      independently. In vivo, PHD3 inhibited tumour growth by abrogation of tumour 
      angiogenesis. CONCLUSION: Our results indicate essential functions of PHD3 in 
      tumour growth, apoptosis and angiogenesis and through HIF-1-dependent and 
      HIF-1-independent pathways.
FAU - Su, Y
AU  - Su Y
AD  - Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 
      Heidelberg 69120, Germany.
FAU - Loos, M
AU  - Loos M
FAU - Giese, N
AU  - Giese N
FAU - Hines, O J
AU  - Hines OJ
FAU - Diebold, I
AU  - Diebold I
FAU - Gorlach, A
AU  - Gorlach A
FAU - Metzen, E
AU  - Metzen E
FAU - Pastorekova, S
AU  - Pastorekova S
FAU - Friess, H
AU  - Friess H
FAU - Buchler, P
AU  - Buchler P
LA  - eng
PT  - Journal Article
DEP - 20101026
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Annexin A5)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 1.13.11.- (Dioxygenases)
RN  - EC 1.14.11.29 (EGLN3 protein, human)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Adenocarcinoma/pathology/surgery
MH  - Animals
MH  - Annexin A5/analysis
MH  - Apoptosis
MH  - Carcinoma, Pancreatic Ductal/enzymology/pathology/surgery
MH  - Caspase 3/metabolism
MH  - Cell Differentiation
MH  - Cell Line, Tumor
MH  - Dioxygenases/*genetics/physiology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/physiology
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases
MH  - Mice
MH  - Neoplasm Invasiveness/genetics/pathology
MH  - Neovascularization, Pathologic/*pathology
MH  - Pancreatic Neoplasms/enzymology/*pathology/surgery
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/genetics
MH  - RNA, Neoplasm/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transplantation, Heterologous
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A/analysis
PMC - PMC2990580
EDAT- 2010/10/28 06:00
MHDA- 2011/03/02 06:00
PMCR- 2011/11/09
CRDT- 2010/10/28 06:00
PHST- 2010/10/28 06:00 [entrez]
PHST- 2010/10/28 06:00 [pubmed]
PHST- 2011/03/02 06:00 [medline]
PHST- 2011/11/09 00:00 [pmc-release]
AID - 6605936 [pii]
AID - 10.1038/sj.bjc.6605936 [doi]
PST - ppublish
SO  - Br J Cancer. 2010 Nov 9;103(10):1571-9. doi: 10.1038/sj.bjc.6605936. Epub 2010 
      Oct 26.