Document Detail

A new, lineage specific, autoup-regulation mechanism for human glucocorticoid receptor gene expression in 697 pre-B-acute lymphoblastic leukemia cells.
MedLine Citation:
PMID:  21084380     Owner:  NLM     Status:  MEDLINE    
Glucocorticoid (GC) steroid hormones induce apoptosis in acute lymphoblastic leukemia (ALL). Autoup-regulation of human GC receptor (hGR) levels is associated with sensitivity to GC-mediated apoptosis. Among the major hGR promoters expressed in 697 pre-B-ALL cells (1A, 1B, 1C, and 1D), only promoters 1C and 1D are selectively activated by the hormone. Promoter 1B is unresponsive, and promoter 1A is down-regulated by dexamethasone (Dex) in 697 cells, whereas they are both up-regulated in CEM-C7 T-ALL cells. Autoup-regulation of promoter 1C and 1D in 697 cells requires sequences containing GC response units (GRUs) (1C GRU, -2915/-2956; 1D GRU, -4525/-4559) that were identified previously in CEM-C7 cells. These GRUs potentially bind GR, c-myeloblastosis (c-Myb), and E-twenty six (Ets) proteins; 697 cells express high levels of c-Myb protein, as well as the E-twenty six family protein members, PU.1 and Spi-B. Dex treatment in 697 cells elevates the expression of c-Myb and decreases levels of both Spi-B and PU.1. Chromatin immunoprecipitation assays revealed the specific recruitment of GR, c-Myb, and cAMP response element-binding protein binding protein to the 1C and 1D GRUs upon Dex treatment, correlating to observed autoup-regulated activity in these two promoters. These data suggest a hormone activated, lineage-specific mechanism to control the autoup-regulation of hGR gene expression in 697 pre-B-ALL cells via steroid-mediated changes in GR coregulator expression. These findings may be helpful in understanding the mechanism that determines the sensitivity of B-ALL leukemia cells to hormone-induced apoptosis.
Chuan-dong Geng; Wayne V Vedeckis
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-17
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  25     ISSN:  1944-9917     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-03     Completed Date:  2011-04-11     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  44-57     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Apoptosis / drug effects
Base Sequence
Cell Lineage / genetics*
Chromatin Immunoprecipitation
Dexamethasone / pharmacology
Gene Expression Regulation, Leukemic* / drug effects
Models, Biological
Molecular Sequence Data
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*,  pathology
Promoter Regions, Genetic / genetics
Protein Binding / drug effects
Proto-Oncogene Proteins c-myb / metabolism
RNA, Messenger / genetics,  metabolism
Receptors, Glucocorticoid / genetics*,  metabolism
Transcription Factors / metabolism
Up-Regulation / drug effects,  genetics*
Grant Support
Reg. No./Substance:
0/NR3C1 protein, human; 0/Proto-Oncogene Proteins c-myb; 0/RNA, Messenger; 0/Receptors, Glucocorticoid; 0/Transcription Factors; 7S5I7G3JQL/Dexamethasone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Expression and regulation of corticotropin-releasing factor receptor type 2? in developing and matur...
Next Document:  Signaling from the human melanocortin 1 receptor to ERK1 and ERK2 mitogen-activated protein kinases ...