PMID- 16517099
OWN - NLM
STAT- MEDLINE
DCOM- 20060623
LR  - 20131121
IS  - 0378-1119 (Print)
IS  - 0378-1119 (Linking)
VI  - 372
DP  - 2006 May 10
TI  - Identification and characterization of the human retinoid X receptor alpha gene 
      promoter.
PG  - 118-27
AB  - Retinoid X receptors (RXRs) comprise a family of nuclear retinoid activated 
      transcription factors that are members of the steroid hormone receptor 
      superfamily. RXRs are obligate heterodimerization partners with several other 
      hormone receptor family members, making them critical mediators of a wide range 
      of signaling pathways. Retinoids have been used successfully for the prevention 
      of a number of epithelial cancers, including skin squamous cell carcinoma (SCC). 
      The reduced expression levels of retinoid receptors including RXRalpha, the 
      predominant RXR expressed in skin, is associated with malignancy in skin SCC. In 
      order to study the regulation of RXRalpha in skin SCC carcinogenesis we have 
      previously mapped the majority of the human RXRalpha gene. In the present study 
      we have identified its first exon and promoter region. Exon 1, which contains the 
      translation start site, is located in a highly G+C rich region of the genome at 
      least 58 kb centromeric from exon 2. The promoter region itself is unusually G+C 
      rich (75% G+C in 1200 bp of upstream sequence), has 17 putative SP1 transcription 
      factor binding sites and no TATA or CAAT boxes. Transient transfection 
      experiments with RXRalpha promoter-luciferase reporter constructs in SRB12-p9 
      skin SCC cells, as well as with PC3 prostate carcinoma cells, revealed that 
      RXRalpha transcription is relatively weak compared to the positive control 
      thymidine kinase (TK) promoter and is stimulated by treatment with all-trans 
      retinoic acid (ATRA), the biologically active form of vitamin A. These results 
      indicate that the RXRalpha gene is transcribed at stable levels, similar to most 
      housekeeping genes, and its transcription is regulated by ATRA. In addition, the 
      5' untranslated region of RXRalpha is highly G+C rich, resulting in a potentially 
      stable folding pattern, that would place RXRalpha amongst a group of genes that 
      are subject to regulation at the translational level.
FAU - Li, Guojun
AU  - Li G
AD  - Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson 
      Cancer Center, Houston, Texas 77030, USA.
FAU - Yin, Weihong
AU  - Yin W
FAU - Chamberlain, Robert
AU  - Chamberlain R
FAU - Hewett-Emmett, David
AU  - Hewett-Emmett D
FAU - Roberts, Jennifer N
AU  - Roberts JN
FAU - Yang, Xiulan
AU  - Yang X
FAU - Lippman, Scott M
AU  - Lippman SM
FAU - Clifford, John L
AU  - Clifford JL
LA  - eng
GR  - 1R29 CA78560/CA/NCI NIH HHS/United States
GR  - CA57730/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060306
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (RNA, Messenger)
RN  - 0 (Retinoid X Receptor alpha)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Base Composition/genetics
MH  - Base Sequence
MH  - Exons/genetics
MH  - Gene Expression Regulation/drug effects
MH  - Genome, Human/genetics
MH  - Humans
MH  - Mice
MH  - Nucleic Acid Conformation
MH  - Physical Chromosome Mapping
MH  - Promoter Regions, Genetic/*genetics
MH  - RNA, Messenger/chemistry/genetics/metabolism
MH  - Regulatory Sequences, Nucleic Acid/genetics
MH  - Retinoid X Receptor alpha/*genetics
MH  - Sequence Analysis, DNA
MH  - Transcription Initiation Site
MH  - Transcription, Genetic
MH  - Tretinoin/pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2006/03/07 09:00
MHDA- 2006/06/24 09:00
CRDT- 2006/03/07 09:00
PHST- 2005/08/28 00:00 [received]
PHST- 2005/12/17 00:00 [revised]
PHST- 2005/12/20 00:00 [accepted]
PHST- 2006/03/07 09:00 [pubmed]
PHST- 2006/06/24 09:00 [medline]
PHST- 2006/03/07 09:00 [entrez]
AID - S0378-1119(06)00021-7 [pii]
AID - 10.1016/j.gene.2005.12.027 [doi]
PST - ppublish
SO  - Gene. 2006 May 10;372:118-27. doi: 10.1016/j.gene.2005.12.027. Epub 2006 Mar 6.