PMID- 20727020
OWN - NLM
STAT- MEDLINE
DCOM- 20110118
LR  - 20131121
IS  - 1365-2559 (Electronic)
IS  - 0309-0167 (Linking)
VI  - 57
IP  - 3
DP  - 2010 Sep
TI  - DNA methylation analysis of the HIF-1alpha prolyl hydroxylase domain genes PHD1, 
      PHD2, PHD3 and the factor inhibiting HIF gene FIH in invasive breast carcinomas.
PG  - 451-60
LID - 10.1111/j.1365-2559.2010.03633.x [doi]
AB  - AIMS: Hypoxia-inducible factor-1 (HIF-1) activity is regulated by prolyl 
      hydroxylase (PHD1, PHD2, PHD3) and factor inhibiting HIF-1 (FIH) that target the 
      alpha subunit of HIF-1 (HIF-1alpha) for proteosomal degradation. We hypothesised that the 
      elevated HIF-1alpha level is due in some tumours to epigenetic silencing by DNA 
      hypermethylation of the promoter region of one or more of the PHDs and FIH genes. 
      The aims were to define the presence or absence of promoter methylation of PHDs 
      and FIH in cell lines of various sources and breast carcinomas and, if present, 
      determine its effect on mRNA and protein expression. METHODS AND RESULTS: Tumour 
      cell lines (n = 20) and primary invasive breast carcinomas (n = 168) were 
      examined for promoter region DNA methylation using methylation-sensitive 
      high-resolution melting. There was evidence of PHD3 but not of PHD1, PHD2 or FIH 
      DNA methylation in breast cancer (SkBr3) and leukaemic (HL60 and CCRF-CEM) cell 
      lines, but there was no evidence of methylation in any of 168 breast cancers. 
      Only the high-level PHD3 methylation seen in leukaemic cell lines correlated with 
      absent mRNA and protein expression. CONCLUSIONS: Methylation-induced epigenetic 
      silencing of PHD1, PHD2, PHD3 and FIH is unlikely to underlie up-regulated HIF-1alpha 
      expression in human breast cancer but may play a role in other tumour types.
CI  - (c) 2010 Blackwell Publishing Limited.
FAU - Huang, Katie T
AU  - Huang KT
AD  - Department of Pathology, Molecular Pathology Research and Development Laboratory, 
      Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.
FAU - Mikeska, Thomas
AU  - Mikeska T
FAU - Dobrovic, Alexander
AU  - Dobrovic A
FAU - Fox, Stephen B
AU  - Fox SB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100819
PL  - England
TA  - Histopathology
JT  - Histopathology
JID - 7704136
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.13.11.- (Dioxygenases)
RN  - EC 1.14.11.- (HIF1AN protein, human)
RN  - EC 1.14.11.2 (EGLN1 protein, human)
RN  - EC 1.14.11.2 (Procollagen-Proline Dioxygenase)
RN  - EC 1.14.11.29 (EGLN2 protein, human)
RN  - EC 1.14.11.29 (EGLN3 protein, human)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
SB  - IM
MH  - Breast Neoplasms/enzymology/*genetics
MH  - Carcinoma/enzymology/*genetics
MH  - DNA Methylation
MH  - Dioxygenases/*genetics
MH  - Female
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases
MH  - Mixed Function Oxygenases
MH  - Nuclear Proteins/*genetics
MH  - Procollagen-Proline Dioxygenase/*genetics
MH  - RNA, Messenger/metabolism
MH  - Repressor Proteins/*genetics
MH  - Transcription Factors/genetics/metabolism
EDAT- 2010/08/24 06:00
MHDA- 2011/01/19 06:00
CRDT- 2010/08/24 06:00
PHST- 2010/08/24 06:00 [entrez]
PHST- 2010/08/24 06:00 [pubmed]
PHST- 2011/01/19 06:00 [medline]
AID - HIS3633 [pii]
AID - 10.1111/j.1365-2559.2010.03633.x [doi]
PST - ppublish
SO  - Histopathology. 2010 Sep;57(3):451-60. doi: 10.1111/j.1365-2559.2010.03633.x. 
      Epub 2010 Aug 19.