Document Detail

Hox proteins activate the IGFBP-1 promoter and suppress the function of hPR in human endometrial cells.
MedLine Citation:
PMID:  12489992     Owner:  NLM     Status:  MEDLINE    
Previous studies have shown that progestin activates the transcription of IGFBP-1 (insulin-like growth factor binding protein-1). Four regions in the IGFBP-1 promotor have been identified to enhance the transcription. Two of the regions, located at -73 to -65 bp and -319 to -311 bp formed identical DNA-protein complexes with the nuclear extracts of endometrial stromal/decidual cells. To identify the binding protein(s) in endometrial cells that interact with these two regions, we have used the TGTCAATTA repeats (-319 to -11 bp of the IGFBP-1 promoter) to screen the human decidual cDNA library by yeast one-hybrid system. We found that Hox A10, HoxA11, HoxB2, HoxB4, and HoxD11 interacted with the TGTCAATTA repeats in yeast cells. Among these hox genes, the full-length coding region of HoxA10, HoxA11, and HoxB4 were used for functional analysis in three types of endometrial cells, undifferentiated endometrial stromal cells, decidual cells (differentiated stromal cells) and endometrial adenocarcinoma cell line (HEC1-B). All these endometrial cells produce IGFBP-1. Transient transfection assay showed that HoxA10 expression vector increased the promoter activity (the IGFBP-1 proximal promoter containing TGC/TCAATTA and two functional PRE sites) in endometrial stromal cells and in HEC-1B cells, but not in decidual cells. HoxB4 enhanced the promoter activity only in decidual cells, while HoxA11 had no apparent effect in all three types of cells. To evaluate whether Hox proteins would interact with progesterone receptor (hPR), cells were transfected with the promoter construct, Hox and hPR expression vectors. hPR alone activated the IGFBP-1 promoter activity, but expression of Hox gene suppressed the activation. Hox proteins also suppressed the hPR enhanced promoter activities of MMTV (containing consensus-PRE sites) and glycodelin (GdA, containing Sp1 site which mediates the hPR function). These data showed that Hox genes selectively activate the transcription of the IGFBP-1 and GdA genes in different types of endometrial cells. Hox genes, however, suppress the hPR enhanced activities. In addition, we found that HoxB4 expression was induced by estrogen and progestin. Other investigators have shown that HoxA10 and 11 were stimulated by progestin. These findings show that Hox proteins are molecular mediators of the steroid hormones during endometrial cell development.
Jiaguo Gao; James Mazella; Linda Tseng
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  DNA and cell biology     Volume:  21     ISSN:  1044-5498     ISO Abbreviation:  DNA Cell Biol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-12-19     Completed Date:  2003-01-15     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9004522     Medline TA:  DNA Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  819-25     Citation Subset:  IM    
Department of Obstetrics and Gynecology, School of Medicine, State University of New York at Stony Brook, Stony Brook, New York 11794-8091, USA.
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MeSH Terms
Decidua / metabolism*
Estrogens / metabolism
Gene Library
Homeodomain Proteins / genetics*,  metabolism
Insulin-Like Growth Factor Binding Protein 1 / genetics*,  metabolism
Progesterone / metabolism
Promoter Regions, Genetic
Receptors, Progesterone / metabolism*
Two-Hybrid System Techniques
Reg. No./Substance:
0/Estrogens; 0/Homeodomain Proteins; 0/Insulin-Like Growth Factor Binding Protein 1; 0/Receptors, Progesterone; 57-83-0/Progesterone

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