PMID- 15352172
OWN - NLM
STAT- MEDLINE
DCOM- 20050222
LR  - 20161124
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 93
IP  - 1
DP  - 2004 Sep 1
TI  - Hypoxia-induced erythropoietin expression in human neuroblastoma requires a 
      methylation free HIF-1 binding site.
PG  - 153-61
AB  - The glycoprotein hormone Erythropoietin (EPO) stimulates red cell production and 
      maturation. EPO is produced by the kidneys and the fetal liver in response to 
      hypoxia (HOX). Recently, EPO expression has also been observed in the central 
      nervous system where it may be neuroprotective. It remained unclear, however, 
      whether EPO is expressed in the peripheral nervous system and, if so, whether a 
      neuronal phenotype is required for its regulation. Herein, we report that EPO 
      expression was induced by HOX and a HOX mimetic in two cell lines derived from 
      neuroblastoma (NB), a tumor of the peripheral nervous system. Both cell lines 
      with inducible EPO expression, SH-SY5Y and Kelly cells, expressed typical 
      neuronal markers like neuropeptide Y (NPY), growth-associated protein-43 
      (GAP-43), and neuron-specific enolase (ENO). NB cells with a more epithelial 
      phenotype like SH-SHEP and LAN-5 did not show HOX inducible EPO gene regulation. 
      Still, oxygen sensing and up-regulation of hypoxia-inducible factor-1 (HIF-1) 
      were intact in all cell lines. We found that CpG methylation of the HIF binding 
      site (HBS) in the EPO gene 3' enhancer was only present in the SH-SHEP and LAN-5 
      cells but not in SH-SY5Y and Kelly cells with regulated EPO expression. The 
      addition of recombinant EPO to all NB cells, both under normoxic and hypoxic 
      conditions, had no effect on cell proliferation. We conclude that the ability to 
      respond to HOX with an increase in EPO expression in human NB may depend on CpG 
      methylation and the differentiation status of these embryonic tumor cells but 
      does not affect the proliferative characteristics of the cells.
FAU - Rossler, Jochen
AU  - Rossler J
AD  - Department of Pediatric Hematology, Oncology and Endocrinology, Children's 
      Hospital, 45122 Essen, Germany. roessler@kikli.ukl.uni-freiburg.de
FAU - Stolze, Ineke
AU  - Stolze I
FAU - Frede, Stilla
AU  - Frede S
FAU - Freitag, Patricia
AU  - Freitag P
FAU - Schweigerer, Lothar
AU  - Schweigerer L
FAU - Havers, Werner
AU  - Havers W
FAU - Fandrey, Joachim
AU  - Fandrey J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Erythropoietin)
RN  - 0 (Transcription Factors)
RN  - 11096-26-7 (Erythropoietin)
SB  - IM
MH  - Binding Sites
MH  - Blotting, Western
MH  - Cell Differentiation
MH  - CpG Islands
MH  - *DNA Methylation
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Erythropoietin/*genetics
MH  - Gene Expression Regulation
MH  - Helix-Loop-Helix Motifs
MH  - Humans
MH  - Hypoxia/*metabolism
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Neuroblastoma/*metabolism/pathology
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Peripheral Nervous System Neoplasms/*metabolism/pathology
MH  - Receptors, Erythropoietin/metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2004/09/08 05:00
MHDA- 2005/02/23 09:00
CRDT- 2004/09/08 05:00
PHST- 2004/09/08 05:00 [pubmed]
PHST- 2005/02/23 09:00 [medline]
PHST- 2004/09/08 05:00 [entrez]
AID - 10.1002/jcb.20133 [doi]
PST - ppublish
SO  - J Cell Biochem. 2004 Sep 1;93(1):153-61. doi: 10.1002/jcb.20133.