© 2000 American Heart Association, Inc.
Molecular Medicine |
Competition for p300 Regulates Transcription by Estrogen Receptors and Nuclear Factor-
B in Human Coronary Smooth Muscle Cells
From the Cardiology Branch (E.S., R.O.C.) and Pathology Section (Z-X.Y., K.T., V.J.F.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Correspondence to Edith Speir, National Institutes of Health, Building 10, Room 7B15, 10 Center Dr, Bethesda, MD 20892-1650. E-mail speire{at}nih.gov
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Abstract—Previous studies suggest that estrogen may prevent expression of cell adhesion molecules implicated in vascular inflammation associated with atherosclerosis. We demonstrate the interaction and reciprocal interference of estrogen receptors (ERs) with p65, the nuclear factor-
B component, in smooth muscle cells that express ER
and
ERß after exposure to 17ß-estradiol for 48 to 72 hours. ER and p65
do not associate directly, as shown by lack of coprecipitation, but
instead compete for limiting amounts of p300, a close relative of the
CREB-binding protein. Overexpressed p300 significantly reduced the
inhibitory effect of ER on p65-dependent transcription as well as the
inhibitory effect of p65 on ER-dependent transcription. These actions
were ligand-dependent. The expression of both ER and nuclear
factor-B–dependent reporter genes was partially rescued from ER/p65
mutual inhibition by transient transfection of smooth muscle cells with
a p300 expression vector. These actions of 17ß-estradiol may play an
important role in the cytokine-induced expression of immune and
inflammatory genes implicated in
atherogenesis.
Key Words: estrogen receptors /ß • intercellular adhesion molecule-1 • nuclear factor-B • transcriptional coactivator p300 • vascular smooth muscle cells
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Estrogen replacement therapy in postmenopausal women is associated with a 40% to 50% reduction in the risk of coronary artery disease.1 Although a substantial portion of these effects may be mediated through changes in serum lipids, other mechanisms also are likely to be involved, as suggested by inhibition of expression of cell adhesion molecules implicated in atherosclerosis.2 Estrogen receptors (ERs) are sequence-specific DNA-binding transcription factors that alter patterns of gene expression in response to their ligand.3 Their transcriptional activity can be stimulated or inhibited by interaction of steroid receptors with other transcription factors. In particular, glucocorticoid receptors have recently been shown to interact with p65/RelA, a component of nuclear factor-
B (NF-B), which in
turn promotes transcription of genes that encode inflammatory
proteins.4 In most cells,
including vascular smooth muscle cells (SMCs), NF-B is sequestered
in the cytoplasm and is activated by a variety of stimuli, including
viral infection and cytokines such as tumor necrosis factor
(TNF).5 NF-B is
important in cytomegalovirus (CMV)-induced viral and cellular gene
expression, and CMV nucleic acid sequences are frequently found in
arterial SMCs in
situ.6 7 8
We have recently shown that estradiol has antioxidant
effects that interfere with CMV-induced signaling of viral and cellular
gene expression in infected SMCs. These beneficial effects were
probably attributable to a direct action, because ER subtypes were
undetectable in these SMCs. We now report that coronary SMCs express
functional estrogen receptors (ER and ERß) after exposure to
17ß-estradiol (E2) for 72 hours and that these
receptors affect transcriptional activation of inflammatory genes by
NF-B.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Cells and Reagents
Human coronary SMCs (Biowhittaker) from a female (age 38) and male (age 58) donor were grown as described.7 COS-1 cells were from American Type Culture Collection (CRL-1650). TNF
and the TNF
Direct kit were from Roche and Intergen, respectively. ER antibodies
were from Santa Cruz Biotechnology. The following plasmids have been
described before: 3XB-CAT and 3XB
mutant-CAT.7 The following
plasmids were gifts: pMT2T65 and pMT2Tp50 (U. Siebenlist, National
Institute of Allergy and Infectious Diseases, NIH),
ERE2-TATA-CAT and pER (B. Katzenellenbogen, University of Illinois,
Champaign-Urbana, Ill), and human ERß plasmid (S. Ali,
Imperial College of Medicine, London, UK). The intercellular adhesion
molecule-1 (ICAM-1)–CAT constructs (-277/+1 and -182/+1) were from
S.W. Caughman,9 (Emory
University, Atlanta, Ga), and the p300 coactivator was from G. Nabel
(Vaccine Research Center, National Institutes of Health, Bethesda, Md).
E2 was obtained from Sigma, and ICI 782,780 was
from Zeneca Pharmaceuticals.
Immunocytochemistry
SMCs were grown in 4-chamber coverslips for 6 hours;
every 24 hours thereafter, the medium was changed to phenol red-free
EBM (Clonetics) containing 2.5% charcoal-filtered serum and
E2 (10 nmol/L). At 72 hours, SMCs were fixed
with methanol at -10°C and treated overnight at 4°C with
antibodies against ER (sc-8002 and sc-8005) 20 µg/mL or ERß
(sc-6822 and sc-6820) 10 µg/mL and proliferating cell nuclear
antigen (PCNA) 5 µg/mL followed by the appropriate secondary
antibodies and FITC-conjugated or Texas red–conjugated streptavidin.
The experiments were repeated 5 times. For controls, we used antibodies
preadsorbed with their immunizing peptides or nonimmune IgG. Nuclei
were counterstained with 4,[prime]6-diamidino-2-phenylindole
dihydrochloride (DAPI) 0.1 µg/mL (Sigma) (blue) for 15 minutes. MCF-7
cells from American Type Culture Collection were grown in phenol-red
free medium and served as positive controls. We also performed
immunostaining for ICAM-1 using biotinylated anti-ICAM antibodies (R&D
Systems) and fluorescein-conjugated streptavidin.
Immunoblots
Immunoblots for ER were performed with lysates of
whole SMCs pretreated with E2 (10 nmol/L for 72
hours). Nuclear extracts of SMCs treated with TNF and with or
without E2 (1 or 10 nmol/L) were immunoblotted
to determine the effect of E2 on p65 and p50
translocation (antibodies sc-109 and sc-7178 at 2 µg/mL, Santa Cruz).
Nuclear extracts were prepared as described
elsewhere.7 Two separate
experiments were performed.
Transfections and CAT Assays
SMCs were grown to 90% confluence in 100-mm
dishes and transfected 20 hours later with reporter constructs
ICAM-1-CAT, B-deleted ICAM-1-CAT, 3XB-CAT, 3XmutB-CAT, and
ERE2-CAT or cotransfected with plasmids expressing the B proteins
p50 (0.1 µg) and p65 (0.01 to 1 µg), the ER plasmids (ER and
ERß) 0.01 to 0.5 µg, and the p300 cofactor plasmid (1 to 2
µg). DOTAP
(N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammoniummethyl-sulfate;
Roche) lipofection agent was used as described
previosuly.7 Three
experiments were performed with each combination.
Statistical Analysis
All CAT assays were performed in triplicate with
separate cell cultures. Data are presented as mean±SD. One way ANOVA
analysis with Tukey-Kramer multiple comparisons test was performed
using Instat 3 Software.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Immunocytochemistry and Immunoblotting for ER
and ERß ExpressionERs were not detectable in these SMCs (at passage 4, the lowest passage available). In SMCs kept in medium containing charcoal-filtered serum (2.5%) and E2 (10 nmol/L) or vehicle (0.1% ethanol) for 48 to 72 hours, ERs were detectable in E2-treated (but not in vehicle-treated) cells by both immunocytochemistry and immunoblotting. ER
and ERß were immunolocalized to the cytoplasm and perinuclear
area of SMCs from both the female
(Figures 1a
through 1d) and male donor. In both cell types,
ERß was expressed in higher amounts than ER, and exposure of cells
to antibodies preadsorbed with their immunizing peptides abolished the
staining. Single staining of SMCs with antibodies to ER and PCNA and
dual staining for ERß and PCNA showed localization of ER to the
cytosol and of PCNA to the nuclei
(Figures 1e through 1h). MCF-7 breast cancer cells, which
express both ER and
ERß,10 11
served as positive controls
(Figures 1i through 1l). SMC lysates were immunoblotted with
anti-ER and anti-ERß antibodies after exposure of cells to
E2 for 72 hours
(Figure 2).
|
|
SMCs Express Functional ERs
To determine if these receptors (above) are competent,
we transfected SMCs with a reporter construct containing 2 estrogen
receptor–responsive elements (ERE2-CAT). Cells transfected with
ERE2-CAT had background CAT activity, but treatment with
E2 (10 nmol/L and 100 nmol/L) caused a
dose-dependent increase in CAT activity
(Figure 3).
|
Effect of E2 on NF-B
Translocation
Pretreatment with E2 (1 or 10
nmol/L) for 72 hours and then with TNF for 1 hour resulted in
translocation of NF-B to the nucleus. E2
treatment did not interfere with NF-B nuclear translocation, as
shown by immunoblotting of nuclear extracts
(Figure 4).
|
Effect of E2 on
Activation of TNF-Dependent ICAM-1-CAT
SMCs exposed to TNF (2 ng/mL) for 1 hour express
ICAM-1 mRNA, and E2 treatment inhibits ICAM-1
mRNA at 3 hours.12 We
examined whether E2/ER can affect ICAM-1 message
via transcriptional interference. In cells transfected with the
reporter ICAM-1-CAT (-277/+1; 2 µg), treatment with TNF (2
ng/mL) for 1 hour caused a 4-fold increase in ICAM-CAT activity. This
was attenuated dose-dependently by pretreatment with
E2 for 48 hours and an additional dose of
E2 for 24 hours after TNF exposure
(Figure 5).
|
ER Interferes with p65-Dependent Activation
of ICAM-1-CAT
To determine whether E2 inhibits
NF-B and whether this effect of E2 is
ER-dependent, we cotransfected SMCs with ICAM-1-CAT, p65 or p50, and
ER expression vectors
(Figure 6A). ICAM-1-CAT activity was increased 5.5-fold by
p65 but not by p50. ER at 0.5 µg completely blocked p65 (0.1 µg)
transcriptional activity but only partially blocked activity (3-fold)
of 10-fold higher p65 concentrations (1 µg). CAT activity was
dependent on the intact NF-B–sequence, because SMCs cotransfected
with p65 and NF-B–deleted ICAM-1-CAT lacked activity. These effects
were similar in SMCs from both a female
(Figure 6B) and male donor and were ligand-dependent: ER
did not block p65-dependent activation in the absence of
E2 (not shown). Furthermore, repression by
E2 /ER was rescued by the ER blocker ICI
782,780. SMCs were treated with E2 (10 nmol/L)
for 48 hours before transfection and for 24 hours at 15 hours after
transfection.
|
Mutual Repression of ER and ERß and
p65-Dependent Transcription
The ICAM-1 promoter has binding sites for transcription
factors other than NF-B,9
which could influence the interaction of ERs with p65. Therefore, we
cotransfected SMCs with a reporter containing 3 NF-B–binding sites
only or with a reporter with mutated NF-B elements (3XB-CAT and
3XmB-CAT) and with p65 and ER expression vectors. CAT activity was
increased 6- to 10-fold by p65, and this was dependent on intact
NF-B sites. This was inhibited by 64% by 0.1 µg of ER and by
90% by 0.5 µg of ER. Again, transfection of 10-fold more p65
partially rescued p65-induced transcription. SMCs transfected with the
mutated reporter did not respond; cotransfection of 3XmB-CAT with
p65, p65, and ER or with p65 and ERß did not yield any
transcriptional activity. Because SMCs seem to express more ERß than
ER, the experiment was repeated using an ERß expression vector. As
expected, p65 activated its cognate promoter, and overexpressed ERß
(0.1 and 0.5 µg) attenuated p65-induced CAT activity by 50% and
80%, respectively, whereas cells with the mutated reporter lacked any
response. SMCs were treated with E2 (10 nmol/L)
for 48 hours before transfection and for 15 hours after transfection.
We also transfected SMCs with an ER-responsive ERE-CAT reporter and
with ER or p65 expression vectors. Cotransfection of the reporter with
ER (200 ng) caused a small increase in CAT activity (2.1-fold),
whereas addition of E2 (10 nmol/L) resulted in a
9-fold activation. When ER was cotransfected with p65 in the
presence of E2, the ER-induced CAT transcription
was reduced by 40%. Addition of ICI 182,780 together with
E2 abrogated this interaction. ERß
cotransfection and E2 treatment caused 4-fold
transcriptional activation, and cotransfection with p65 and
E2 treatment caused a 50% repression of
ERß-dependent transcription. These results suggest that both
transcriptional activation by ER and repression by p65 are
ligand-dependent, as shown by the lack of activation in the absence of
E2 and by the reversal of the effect of
E2/ER in the presence of the complete ER blocker
ICI 182, 780 (not shown).
Immunoprecipitation of ER and p65
(COS-1)
To examine a possible direct protein-protein
interaction between ER and p65, which could explain mutual
transcriptional interference, we performed immunoprecipitation of SMCs
transfected ER and p65. Several experiments and subsequent
immunoblotting gave variable and unsatisfactory results because of very
low protein expression in SMCs. However, we found that COS-1 cells,
when transfected with ER or ERß, consistently expressed detectable
amounts of ER and p65. We therefore cotransfected COS-1 cells with both
p65 and ER and precipitated the cell lysates with anti-p65 antibodies,
which were positive when blotted with p65 antibodies but negative
when blotted with anti-ER antibodies. Lysates precipitated with anti-ER
antibody were positive when blotted for ER but negative when blotted
with anti-p65 antibodies. The experiment was repeated 3 times with the
same results. This indicates that direct protein-protein interaction
between p65 and ER is not likely in COS-1 cells.
Role of Coactivator p300 in the Interaction of
ER and p65
Both ER and p65 recruit and interact with the p300
protein
coactivator.13 14
To examine whether mutual transcriptional repression by ER and p65
might be attributable to competition for limited amounts of p300, we
cotransfected SMCs (pretreated for 48 hours with
E2) with ERE-CAT and ER-, ERß-, p65-, or
p300-expression vectors. Cotransfection with p300 did not modify CAT
activity
(Figure 7, bar 2) beyond the 2-fold increase in activity
noted with endogenous ER and estradiol
(Figure 3
). Furthermore, ER or ERß caused 6- or 5-fold
activation
(Figure 7, bars 3 and 7), exogenous p300 had an inhibitory
effect on ER-dependent transcription by 10% and 34% (bars 4 and 8),
and p65 inhibited ER activity by 73% and 67% (bars 5 and 9). The
inhibitory effect of p65 was reduced 50% and 33% by cotransfection of
p300 (bars 6 and 10). Both ER and p65 recruit p300, and by
cotransfecting SMCs with the p65-responsive 3XB-CAT reporter and
vectors for p65, ER, and p300, we determined that the negative
regulation of ER/p65 is reciprocal. P300 overexpression can
significantly reduce repression of p65 transcriptional activity by
ER
(Figure 8). Experiments performed in the absence of
E2 pretreatment showed a lack of adequate
ER/ERE-CAT activation, minimal p300 interaction with ER/p65/ERE-CAT,
and inconsistent interaction of p65/ER/3XB-CAT. In many experiments,
exogenous p300 had little effect on ERE-CAT or 3XB-CAT activation.
However, in a few experiments, transfected p300 caused a 2-fold
increase in CAT activity.
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
We have recently shown by electrophoretic mobility shift assay that treatment for 1 hour with E2 inhibits TNF
-induced NF-B–binding to its cognate
DNA.12 We now demonstrate by
immunoblotting nuclear lysates from SMCs exposed to
E2 for 72 hours that nuclear translocation of
the NF-B subunits p65 and p50 is not inhibited by pretreatment with
E2 for 72 hours. These findings suggest that
E2 and ER affect NF-B–DNA binding. We
additionally found that estrogen inhibits TNF-induced ICAM-1 mRNA
expression in SMCs at 3 hours (not shown). In this study, we asked
whether there might also be ER-dependent effects. We detected both
ER and ERß
(Figure 1); in 5 experiments, both receptors immunolocalized
to the cytoplasm. Clearly, at least some of the ERs were localized to
the nucleus at some point, perhaps transiently, because SMCs
transfected with an ER-responsive reporter (ERE-CAT) responded to
E2 treatment by increased CAT activity. A
positive nuclear reaction for PCNA was found in 60% of SMCs,
indicating that the negative nuclear staining for ER was not
attributable to lack of antibody penetration. Recent reports by other
laboratories also show immunolocalization of functional ERs to the
cytosol of vascular
SMCs.15 16 Of
note, in ER-transfected SMCs and COS-1 cells, receptors immunolocalized
to both nuclei and cytoplasm. It is possible that the conditions of the
transfection experiments (overexpression of ER) may lead to suppression
of the cytosolic retention mechanism.
The mutual transcriptional repression of ER and p65 toward
the ICAM-1, ERE, and NF-B reporters can be reduced by transfecting
with 10-fold excess of the activating transcription factor
(Figure 6A, bar 10). The same is true for the ER/ERE and
p65 interaction (not shown). For 17ß-estradiol–induced
transactivation, the N-terminal A/B domain (AF-1) and the C-terminal
E/F domain of ERs are required. Ligand binding induces functional
synergism between AF-1 and AF-2; the molecular mechanism was only
recently elucidated. Ligand-induced functional synergism between AF-1
and AF-2 is mediated through p300 by its direct binding to both ER
and ERß.17
Estrogen has been implicated not only in vasculoprotective18 but also in proinflammatory processes.19 The particular effect is dependent on tissue and cell type, cell-associated factors and cofactors, ER isotype and number, and gender. Clearly, the modifying cellular factors are different in cells activated by cytokines or in transformed cells.2 19 20
The ER belongs to the nuclear receptor superfamily, and
members of this family are known to exist in a complex of chaperones in
the cytosol. Once activated by the respective ligand, ERs translocate
to the nucleus, where they associate with multiple cofactors. These
cofactors determine the potential transcriptional activation or
repression of target genes by nuclear
receptors.3 21
P300, a histone acetyltransferase, is a close relative of the
CREB-binding protein and has been shown to be a component of the
coactivator complex of nuclear receptors as well as of
NF-B.13 14
Some interactions of nuclear receptors with other nuclear proteins,
such as p300 and NF-B, seem to be cell type–specific but are
generally
ligand-dependent.13 21
E2 is essential for activation of endogenous and
transfected ERE
(Figure 7) and is necessary for maximal inhibitory effect on
p65-dependent activation
(Figures 6 and 8). This indicates that p300 interacts with the
ER ligand–binding domain.
Our findings suggest that interaction between ER and
ERß and NF-B may depend on the state of activation of SMCs. In the
presence of stressors such as CMV and TNF, activated NF-B may
suppress E2- and ER-dependent transcription by
binding limiting amounts of p300. In the absence of potent and
prolonged NF-B activators, ER and ERß have the potential of
inhibiting NF-B by binding the available p300. This has important
implications for the role of estrogen in processes such as vasculitis
and atherogenesis in female
patients.
Received August 18, 2000; revision received September 29, 2000; accepted September 29, 2000.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Lobo RA, Speroff L. International consensus conference on postmenopausal therapy and the cardiovascular system. Fertil Steril. 1994;592–595.
2. Caulin-Glaser T, Watson CA, Pardi R, Bender JR. Effect of 17ß-estradiol on cytokine-induced endothelial cell adhesion molecule expression. J Clin Invest. 1996;98:36–42.[Medline] [Order article via Infotrieve]
3. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM. The nuclear receptor superfamily: the second decade. Cell. 1995;83:835–839.[Medline] [Order article via Infotrieve]
4.
Scheinman RI,
Gualberto A, Jewell CM, Cidlowski JA, Baldwin AS. Characterization of
mechanisms involved in transrepression of NF-B by activated
glucocorticoid receptors. Mol Cell
Biol. 1995;15:943–953.[Abstract]
5.
Baldwin AS. The
NF-B, and I B proteins: new discoveries and insights.
Annu Rev Immunol. 1996;14:649–681.[Medline]
[Order article via Infotrieve]
6.
Speir E, Modali R,
Huang ES, Leon MB, Shawl F, Finkel T, Epstein SE. Potential role of
human cytomegalovirus and p53 interaction in coronary restenosis.
Science. 1994;265:391–394.
7.
Speir E, Yu ZX,
Ferrans VJ, Huang ES, Epstein SE. Aspirin attenuates cytomegalovirus
infectivity and gene expression mediated by cyclooxygenase-2 in
coronary artery smooth muscle cells. Circ
Res. 1998;83:210–216.
8. Melnick JL, Adam E, DeBakey ME. Human cytomegalovirus and atherogenesis. In: Becker Y, Darai G, Huang ES, eds. Frontiers of Virology 2: Molecular Aspects of Human Cytomegalovirus Diseases. New York, NY: Springer Verlag; 1993:80–91.
9.
Degitz K, Li LJ,
Caughman SW. Cloning and characterization of the 5'-transcriptional
regulatory region of the human intercellular adhesion molecule 1 gene.
J Biol Chem. 1991;266:14024–14030.
10. Register TC, Adams MR. Coronary artery and cultured aortic smooth muscle cells express mRNA for both the classical estrogen receptor and the newly described estrogen receptor beta. J Steroid Biochem Mol Biol. 1998;64:187–191.[Medline] [Order article via Infotrieve]
11. Burow ME, Weldon CB, Chiang TC, Tang Y, Collins-Burow BM, Rolfe K, Li S, McLachlan JA, Beckman BS. Differences in protein kinase C and estrogen receptor alpha, beta expression and signaling correlate with apoptotic sensitivity of MCF-7 breast cancer cell variants. Int J Oncol. 2000;16:1179–1187.[Medline] [Order article via Infotrieve]
12. Speir E, Yu ZX, Takeda K, Ferrans VJ, Cannon RO III. Antioxidant effect of estrogen on cytomegalovirus-induced gene expression in coronary artery smooth muscle cells. Circulation. In press.
13.
Hanstein B,
Eckner R, DiRenzo J, Halachmi S, Liu H, Searcy B, Kurokawa R, Brown M.
p300 is a component of an estrogen receptor coactivator complex.
Proc Natl Acad Sci
U S A.. 1996;93:11540–11545.
14.
Perkins ND,
Felzien LK, Betts JC, Leung K, Beach DH, Nabel GJ. Regulation of NF-6B
by cyclin-dependent kinases associated with the p300 coactivator.
Science. 1997;275:523–527.
15. Bayard F, Clamens S, Meggetto F, Blaes N, Delsol G, Faye J-C. Estrogen synthesis, estrogen metabolism, and functional estrogen receptors in rat arterial smooth muscle cells in culture. Endocrinology. 1995;136:1523–1529.[Abstract]
16.
Balica M, Bostrom
K, Shin V, Tillisch K, Demer LL. Calcifying subpopulation of bovine
aortic smooth muscle cells is responsive to 17ß-estradiol.
Circulation. 1997;95:1954–1960.
17.
Kobayashi Y,
Kitamoto T, Masuhiro Y, Watanabe M, Kase T, Metzger D, Yanagisawa J,
Kato S. p300 mediates functional synergism between AF-1 and AF-2 of
estrogen receptor alpha and beta by interacting directly with the
N-terminal A/B domains. J Biol
Chem. 2000;275:15645–15651.
18.
Mendelsohn ME,
Karas RH. The protective Effects of estrogen on the cardiovascular
system. N Engl J Med. 1999;340:1801–1811.
19. Cid MC, Kleinman HK, Grant DS, Schnaper HW, Fauci AS, Hoffman GS. Estradiol enhances leukocyte binding to tumor necrosis factor (TNF)-stimulated endothelial cells via an increase in TNF-induced adhesion molecules E-selectin, intercellular adhesion molecule type-1, and vascular cell adhesion molecule type-1. J Clin Invest. 1994;93:17–25.
20. Nakshatri H, Bhat-Nakshatri P, Martin DA, Goulet RJ, Sledge GW. Constitutive activation of NF-6B during progression of breast cancer to hormone-independent growth. Mol Cell Biol. 1997;17:3629–3639.[Abstract]
21. Chakravarti D, LaMorte VJ, Nelson MC, Nakajima T, Schulman IG, Juguilon H, Montminy M, Evans RM. Role of CBP/P300 in nuclear receptor signaling. Nature. 1996;383:99–103.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  O. Bukulmez, D. B. Hardy, B. R. Carr, R. A. Word, and C. R. Mendelson Inflammatory Status Influences Aromatase and Steroid Receptor Expression in Endometriosis Endocrinology, March 1, 2008; 149(3): 1190 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. W. Nettles, G. Gil, J. Nowak, R. Metivier, V. B. Sharma, and G. L. Greene CBP Is a Dosage-Dependent Regulator of Nuclear Factor-{kappa}B Suppression by the Estrogen Receptor Mol. Endocrinol., February 1, 2008; 22(2): 263 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sunday, C. Osuna, D. N. Krause, and S. P. Duckles Age alters cerebrovascular inflammation and effects of estrogen Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2333 - H2340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Harris Estrogen Receptor-{beta}: Recent Lessons from in Vivo Studies Mol. Endocrinol., January 1, 2007; 21(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Montague, M. G. Hunter, M. A. Gavrilin, G. S. Phillips, P. J. Goldschmidt-Clermont, and C. B. Marsh Activation of Estrogen Receptor-{alpha} Reduces Aortic Smooth Muscle Differentiation Circ. Res., September 1, 2006; 99(5): 477 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Hardman, A. Waite, L. Zeef, M. Burow, T. Nakayama, and G. S. Ashcroft Macrophage Migration Inhibitory Factor: A Central Regulator of Wound Healing Am. J. Pathol., December 1, 2005; 167(6): 1561 - 1574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Grasberger, U. Ringkananont, P. LeFrancois, M. Abramowicz, G. Vassart, and S. Refetoff Thyroid Transcription Factor 1 Rescues PAX8/p300 Synergism Impaired by a Natural PAX8 Paired Domain Mutation with Dominant Negative Activity Mol. Endocrinol., July 1, 2005; 19(7): 1779 - 1791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y Zhou, S Eppenberger-Castori, U Eppenberger, and C C Benz The NF{kappa}B pathway and endocrine-resistant breast cancer Endocr. Relat. Cancer, July 1, 2005; 12(Supplement_1): S37 - S46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Sohn, C. B. Deming, D. C. Johns, H. C. Champion, C. Bian, K. Gardner, and J. J. Rade Regulation of endothelial thrombomodulin expression by inflammatory cytokines is mediated by activation of nuclear factor-kappa B Blood, May 15, 2005; 105(10): 3910 - 3917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Chadwick, S. Chippari, E. Matelan, L. Borges-Marcucci, A. M. Eckert, J. C. Keith Jr., L. M. Albert, Y. Leathurby, H. A. Harris, R. A. Bhat, et al. Identification of pathway-selective estrogen receptor ligands that inhibit NF-{kappa}B transcriptional activity PNAS, February 15, 2005; 102(7): 2543 - 2548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. X. Jin, Y.-W. Leu, S. Liyanarachchi, H. Sun, M. Fan, K. P. Nephew, T. H.-M. Huang, and R. V. Davuluri Identifying estrogen receptor {alpha} target genes using integrated computational genomics and chromatin immunoprecipitation microarray Nucleic Acids Res., December 17, 2004; 32(22): 6627 - 6635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. McCarty Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy Integr Cancer Ther, December 1, 2004; 3(4): 349 - 380. [Abstract] [PDF]
|
|
|
|
 |
|
 K. H. Seo, H.-S. Lee, B. Jung, H.-M. Ko, J.-H. Choi, S. J. Park, I.-H. Choi, H.-K. Lee, and S.-Y. Im Estrogen Enhances Angiogenesis through a Pathway Involving Platelet-Activating Factor-Mediated Nuclear Factor-{kappa}B Activation Cancer Res., September 15, 2004; 64(18): 6482 - 6488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Hamilton, F.N. Mbai, S. Gupta, and A.A. Knowlton Estrogen, Heat Shock Proteins, and NF{kappa}B in Human Vascular Endothelium Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1628 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Ospina, H. N. Brevig, D. N. Krause, and S. P. Duckles Estrogen suppresses IL-1{beta}-mediated induction of COX-2 pathway in rat cerebral blood vessels Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H2010 - H2019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Harnish, L. M. Albert, Y. Leathurby, A. M. Eckert, A. Ciarletta, M. Kasaian, and J. C. Keith Jr. Beneficial effects of estrogen treatment in the HLA-B27 transgenic rat model of inflammatory bowel disease Am J Physiol Gastrointest Liver Physiol, January 1, 2004; 286(1): G118 - G125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Liu, E.-S. Lee, C. Gajdos, S. T. Pearce, B. Chen, C. Osipo, J. Loweth, K. McKian, A. De Los Reyes, L. Wing, et al. Apoptotic Action of 17{beta}-Estradiol in Raloxifene-Resistant MCF-7 Cells In Vitro and In Vivo J Natl Cancer Inst, November 5, 2003; 95(21): 1586 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Frasor, J. M. Danes, B. Komm, K. C. N. Chang, C. R. Lyttle, and B. S. Katzenellenbogen Profiling of Estrogen Up- and Down-Regulated Gene Expression in Human Breast Cancer Cells: Insights into Gene Networks and Pathways Underlying Estrogenic Control of Proliferation and Cell Phenotype Endocrinology, October 1, 2003; 144(10): 4562 - 4574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Martin-McNulty, D. M. Tham, V. da Cunha, J. J. Ho, D. W. Wilson, J. C. Rutledge, G. G. Deng, R. Vergona, M. E. Sullivan, and Y.-X. Wang 17{beta}-Estradiol Attenuates Development of Angiotensin II-Induced Aortic Abdominal Aneurysm in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1627 - 1632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Adams, D. L. Golden, T. C. Register, M. S. Anthony, J. B. Hodgin, N. Maeda, and J.K. Williams The Atheroprotective Effect of Dietary Soy Isoflavones in Apolipoprotein E-/- Mice Requires the Presence of Estrogen Receptor-{alpha} Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1859 - 1864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Evans, K. Lai, L. J. Shaw, D. C. Harnish, and C. C. Chadwick Estrogen Receptor {alpha} Inhibits IL-1{beta} Induction of Gene Expression in the Mouse Liver Endocrinology, July 1, 2002; 143(7): 2559 - 2570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pfeilschifter, R. Koditz, M. Pfohl, and H. Schatz Changes in Proinflammatory Cytokine Activity after Menopause Endocr. Rev., February 1, 2002; 23(1): 90 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. V. Sharma, M. V. Gurjar, and R. C. Bhalla Genome and Hormones: Gender Differences in Physiology: Selected Contribution: Estrogen receptor-alpha gene transfer inhibits proliferation and NF-kappa B activation in VSM cells from female rats J Appl Physiol, November 1, 2001; 91(5): 2400 - 2406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Sugihara, E. I. Kudryavtseva, V. Kumar, J. J. Horridge, and B. Andersen The POU Domain Factor Skin-1a Represses the Keratin 14 Promoter Independent of DNA Binding. A POSSIBLE ROLE FOR INTERACTIONS BETWEEN Skn-1a AND CREB-BINDING PROTEIN/p300 J. Biol. Chem., August 24, 2001; 276(35): 33036 - 33044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-L. M. Cooke and S. T. Davidge Peroxynitrite increases iNOS through NF-kappa B and decreases prostacyclin synthase in endothelial cells Am J Physiol Cell Physiol, February 1, 2002; 282(2): C395 - C402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Evans, A. Eckert, K. Lai, S. J. Adelman, and D. C. Harnish Reciprocal Antagonism Between Estrogen Receptor and NF-{kappa}B Activity In Vivo Circ. Res., October 26, 2001; 89(9): 823 - 830. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||