PMID- 17932106
OWN - NLM
STAT- MEDLINE
DCOM- 20080709
LR  - 20211020
IS  - 0888-8809 (Print)
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Linking)
VI  - 22
IP  - 2
DP  - 2008 Feb
TI  - CBP Is a dosage-dependent regulator of nuclear factor-kappaB suppression by the 
      estrogen receptor.
PG  - 263-72
AB  - The estrogen receptor (ER) protects against debilitating effects of the 
      inflammatory response by inhibiting the proinflammatory transcription factor 
      nuclear factor-kappaB (NFkappaB). Heretofore cAMP response element-binding 
      protein (CREB)-binding protein (CBP) has been suggested to mediate inhibitory 
      cross talk by functioning either as a scaffold that links ER and NFkappaB or as a 
      required cofactor that competitively binds to one or the other transcriptional 
      factor. However, here we demonstrate that ER is recruited to the NFkappaB 
      response element of the MCP-1 (monocyte chemoattractant protein-1) and IL-8 
      promoters and displaces CBP, but not p65, in the MCF-7 breast cancer cell line. 
      In contrast, ER displaced p65 and associated coregulators from the IL-6 promoter, 
      demonstrating a gene-specific role for CBP in integrating inflammatory and 
      steroid signaling. Further, RNA interference and overexpression studies 
      demonstrated that CBP dosage regulates estrogen-mediated suppression of MCP-1 and 
      IL-8, but not IL-6, gene expression. This work further demonstrates that CBP 
      dosage is a critical regulator of gene-specific signal integration between the 
      ER- and NFkappaB-signaling pathways.
FAU - Nettles, Kendall W
AU  - Nettles KW
AD  - Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, 
      USA. knettles@scripps.edu
FAU - Gil, German
AU  - Gil G
FAU - Nowak, Jason
AU  - Nowak J
FAU - Metivier, Raphael
AU  - Metivier R
FAU - Sharma, Vandana B
AU  - Sharma VB
FAU - Greene, Geoffrey L
AU  - Greene GL
LA  - eng
GR  - R01 CA089489/CA/NCI NIH HHS/United States
GR  - 5R01 CA 89489/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20071011
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.3.1.48 (CREBBP protein, human)
SB  - IM
MH  - Blotting, Northern
MH  - CREB-Binding Protein/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/genetics/metabolism
MH  - Chromatin Immunoprecipitation
MH  - Electrophoretic Mobility Shift Assay
MH  - Estradiol/metabolism
MH  - Estrogen Receptor alpha/genetics/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Immunoprecipitation
MH  - Interleukin-6/genetics
MH  - Interleukin-8/genetics
MH  - Models, Biological
MH  - NF-kappa B/*metabolism
MH  - Polymerase Chain Reaction
MH  - Protein Binding
MH  - Transcription Factor RelA/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC2234588
EDAT- 2007/10/13 09:00
MHDA- 2008/07/10 09:00
PMCR- 2009/02/01
CRDT- 2007/10/13 09:00
PHST- 2007/10/13 09:00 [pubmed]
PHST- 2008/07/10 09:00 [medline]
PHST- 2007/10/13 09:00 [entrez]
PHST- 2009/02/01 00:00 [pmc-release]
AID - me.2007-0324 [pii]
AID - 4179 [pii]
AID - 10.1210/me.2007-0324 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2008 Feb;22(2):263-72. doi: 10.1210/me.2007-0324. Epub 2007 Oct 
      11.