Breast
Prostate
2009/11/20
Mol Cells. 2009 Oct 21. [Epub ahead of
print] Department of Exercise
Science, College of Health Sciences, Ewha Womans University, Seoul,
120-750, Korea, jun@ewha.ac.kr. Although insulin-like growth
factor-I (IGF-I) and androgen receptor (AR) are well known effectors of
skeletal muscle, the molecular mechanism by which signaling pathways integrating
AR and IGF-I in skeletal muscle cells has not been previously examined. In
this study, the role of PI3K/Akt on IGF-I-induced gene expression and
activation of AR in skeletal muscle cells was investigated. C2C12 cells
were treated with IGF-I in the absence or presence of inhibitors of
PI3K/Akt pathway (LY294002 and Wortmannin). Inhibition of the PI3K/Akt
pathway with LY294002 or Wortmannin led to a significant decrease in
IGF-I-induced AR phosphorylation and total AR protein expression. Furthermore,
IGF-I-induced AR mRNA and skeletal alpha-actin mRNA were blocked by
LY294002 or Wortmannin. Confocal images showed that IGF-I-induced AR
translocation from cytosol to nucleus was inhibited significantly in
response to treatment with LY294002 or Wortmannin. The present results
suggest that modulating effect of IGF-I on AR gene expression and
activation in C2C12 mouse skeletal muscle cells is mediated at least in
part by the PI3K/Akt pathway. PMID: 19855934 [PubMed - as
supplied J Cell Mol Med.
2009 Oct 16. [Epub ahead of print] Peng
Y, Li
Y, Gellert
LL, Zou
X, Wang
J, Singh
B, Xu
R, Chiriboga
L, Daniels
G, Pan
R, Zhang
DY, Garabedian
M, Schneider
R, Wang
Z, Lee
P. Department of Pathology, New
York University School of Medicine, New York, New York. Hormones and their receptors
play an important role in the development and progression of breast
carcinoma. Although the primary focus has been on estrogen and estrogen
receptor (ER), androgen, androgen receptor (AR) and its coactivator(s) have
been implicated in tumorigenesis of ductal carcinoma and warrant further
investigation. Androgen receptor coactivator p44/Mep50 is identified as a
subunit of methylosome complex and lately characterized as an androgen
receptor coactivator that enhances androgen receptor mediated transcription
activity in a ligand-dependent manner. In prostate cancer, p44 is expressed
in the nucleus of benign epithelia and translocated into the cytoplasm in
cancer cells. Furthermore, nuclear expression of p44 inhibits prostate
cancer growth. In this report, we examined the expression and function of
p44 in breast cancer. In addition to being an AR coactivator, p44 also
functions as an ER coactivator. In contrast to findings in prostate cancer,
the expression of p44 shows strong cytoplasmic expression in
morphologically normal terminal ductal lobular units, while nuclear p44 is
observed in both ductal carcinoma in situ (DCIS) and invasive carcinoma.
Further, overexpression of nuclear-localized p44 stimulates proliferation
and invasion in MCF7 breast cancer cells in the presence of estrogen and is
ERalpha-dependent. These findings strongly suggest that p44 plays a role in
mediating the effects of hormones during tumorigenesis in breast. PMID: 19840198 [PubMed EMBO J.2006 Dec 14; [Epub ahead of print] · A novel function of caspase-8 in the regulation
ofandrogen-receptor-driven gene expression · · Qi W,Wu H,Yang L,Boyd
DD,Wang Z. Department of Cancer Biology, The University
ofTexas MD Anderson Cancer Center, Houston, TX, USA. Transcriptional regulation by the androgen receptor(AR)
is critical for male sexual development and prostate cancer. In thisstudy,
we used an expression cloning strategy to identify molecules thatregulate
AR-driven transcription. Screening of a human cDNA libraryresulted in
isolation of caspase-8 (Casp8), an initiator caspase thatmediates
death-receptor-induced apoptosis. Casp8 repressed AR-dependentgene
expression independently of its apoptotic protease activity bydisrupting AR
amino-terminal and carboxy-terminal (N/C) interaction andinhibiting
androgen-induced AR nuclear localization. Protein-proteininteraction
analysis revealed that three motifs in Casp8 specificallyinteracted with
the motifs that are known to be involved in AR N/Cinteraction.
Substitutions of the amino-acid residues critical for AR-Casp8interactions
abolished the Casp8-mediated inhibition of AR transactivation.In addition,
knockdown of Casp8 by RNA interference specifically affectedthe
androgen-dependent expression of AR-targeting genes in LNCaP cells.These
results indicate that Casp8 has a novel function beyond its knownrole in
the mediation of apoptosis. PMID: 17170703 [PubMed - as supplied by publisher] Steroids.2006 Dec 11; [Epub ahead of print] Hic-5/ARA55
a prostatestroma-specific AR coactivator. · Heitzer MD,Defranco DB. Department of Pharmacology, University
ofPittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA
15261,United States. Growth factors and cytokines mediate
communicationbetween the epithelial and stromal compartments of the
prostate. Inprostate cancer (PCa), changes in the spatial arrangements of
the twocompartments (i.e. basement membrane invasion), DNA mutations, or
cellulardedifferentiation (i.e. myofibroblasts) leads to significant
changes ingene expression within both compartments. This results in altered
cytokineand/or growth factor signaling in PCa. Recently, a stromal-specific
androgenreceptor (AR) coactivator, Hic-5/ARA55, has been identified that
may play arole in regulating expression of the growth factor and/or
cytokineexpression in the prostate. Specifically, Hic-5/ARA55 expression
influencesandrogen-induced keratinocyte growth factor (KGF) expression in
WPMY-1prostate stromal cells. Because Hic-5/ARA55's expression is also
altered inPCa, it may play a role in the differential cellular signaling
events thatoccur during tumor progression. PMID: 17166536 [PubMed - as supplied by publisher BiochemBiophys Res Commun.2006 Dec 22; [Epub ahead of print] Signaling
pathway ofnitric oxide production induced by ginsenoside Rb1 in human
aorticendothelial cells: A possible involvement of androgen receptor. · Yu J,Eto M,Akishita M,Kaneko
A,Ouchi Y,Okabe T. Department of Integrated Traditional
Medicine,University of Tokyo Graduate School of Medicine, Tokyo, Japan. Ginsenosides have been shown to stimulate nitric
oxide(NO) production in aortic endothelial cells. However, the
signalingpathways involved have not been well studied in human aortic
endothelialcells. The present study was designed to examine whether
purifiedginsenoside Rb1, a major active component of ginseng could actually
induceNO production and to clarify the signaling pathway in human aorticendothelial
cells. NO production was rapidly increased by Rb1. The rapidincrease in NO
production was abrogated by treatment with nitric oxidesynthetase
inhibitor, L-NAME. Rb1 stimulated rapid phosphorylation of Akt(Ser473),
ERK1/2 (Thr202/Thr204) and eNOS (Ser1177). Rapid phosphorylationof eNOS
(Ser1177) was prevented by SH-5, an Akt inhibitor or wortmannin,PI3-kinase
inhibitor and partially attenuated by PD98059, an upstreaminhibitor for
ERK1/2. Interestingly, NO production and eNOS phosphorylationat Ser1177 by
Rb1 were abolished by androgen receptor antagonist,nilutamide. The results
suggest that PI3kinase/Akt and MEK/ERK pathways andandrogen receptor are
involved in the regulation of acute eNOS activationby Rb1 in human aortic
endothelial cells. PMID: 17196933 [PubMed - as supplied by publisher] MolEndocrinol.2006 Dec 27; [Epub ahead of print] PELP1/MNAR
enhancesandrogen receptor functions through LIM-only coactivator FHL2. · Nair SS,Guo Z,Mueller JM,Koochekpour
S,Qiu Y,Tekmal RR,Schule R,Kumar PMID:17192406
[PubMed - as supplied by publisher]
Insulin-like growth
factor-I-induced androgen receptor activation is mediated by the PI3K/Akt pathway
in C2C12 skeletal muscle cells.
Androgen receptor
coactivator p44/Mep50 in breast cancer growth and invasion.
