PMID- 11050012
OWN - NLM
STAT- MEDLINE
DCOM- 20001211
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 96
IP  - 9
DP  - 2000 Nov 1
TI  - Retinoic acid stimulates erythropoietin gene transcription in embryonal carcinoma 
      cells through the direct repeat of a steroid/thyroid hormone receptor response 
      element half-site in the hypoxia-response enhancer.
PG  - 3265-71
AB  - We have previously reported that expression of the erythropoietin (Epo) gene in 
      mouse embryonal cells was not induced by hypoxia, although hypoxia induced other 
      hypoxia-inducible genes. This study identifies retinoic acid (RA) as an inducer 
      for Epo production in the embryonal carcinoma cell lines P19 and F9. RA induced 
      Epo production through the transcriptional activation of the Epo gene in an 
      oxygen-independent manner. With the use of reporter assays in P19 cells, it is 
      shown that a direct repeat of the nuclear hormone receptor-binding motif 
      separated by a 2-bp spacer (DR-2) in the hypoxia-response enhancer was 
      responsible for the transcriptional activation by RA. Electrophoretic mobility 
      shift assays show that nuclear extracts from P19 cells contained RA receptor 
      complexes that bound to DR-2. In human hepatoma Hep3B cells, an orphan receptor, 
      hepatocyte nuclear factor-4, strongly augmented hypoxic induction of the Epo gene 
      in cooperation with hypoxia-inducible factor-1 (HIF-1) by binding to DR-2, 
      whereas in P19 cells, the interaction of RA receptors with DR-2 was sufficient 
      for RA-induced transcriptional activation of the Epo gene without the requirement 
      of the HIF-1 site. These results suggest that DR-2 regulates expression of the 
      Epo gene by acting as the binding site for different transcription factors in 
      different types of cells.
FAU - Kambe, T
AU  - Kambe T
AD  - Division of Integrated Life Science, Graduate School of Biostudies, Kyoto 
      University, Kyoto, Japan.
FAU - Tada-Kambe, J
AU  - Tada-Kambe J
FAU - Kuge, Y
AU  - Kuge Y
FAU - Yamaguchi-Iwai, Y
AU  - Yamaguchi-Iwai Y
FAU - Nagao, M
AU  - Nagao M
FAU - Sasaki, R
AU  - Sasaki R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Receptors, Steroid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 11096-26-7 (Erythropoietin)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Carcinoma, Embryonal/*genetics
MH  - *Cell Hypoxia
MH  - *Enhancer Elements, Genetic
MH  - Erythropoietin/*genetics
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Genes, Reporter
MH  - Humans
MH  - Luciferases/genetics
MH  - Mice
MH  - Promoter Regions, Genetic
MH  - Receptors, Steroid/*metabolism
MH  - Receptors, Thyroid Hormone/*metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Nucleic Acid
MH  - Transfection
MH  - Tretinoin/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2000/10/26 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/26 11:00
PHST- 2000/10/26 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/26 11:00 [entrez]
AID - S0006-4971(20)48360-0 [pii]
PST - ppublish
SO  - Blood. 2000 Nov 1;96(9):3265-71.