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Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2.
[esophageal squamous cell carcinoma]
Stat
3
alters
the
expression
of
its
downstream
genes
and
is
associated
with
tumor
invasion
and
metastasis
in
several
human
cancers
.
Its
role
in
esophageal
squamous
cell
carcinoma
(
ESCC
)
has
not
been
well
characterized
.
We
examined
the
tumor
sections
of
100
cases
of
ESCC
by
immunohistochemistry
and
observed
significant
overexpression
of
Stat
3
in
the
cytoplasm
of
89
%
of
ESCC
cells
and
of
phosphorylated
Stat
3
(
p
-
Stat
3
)
in
the
nuclei
of
71
%
of
ESCC
when
compare
with
normal
esophageal
mucosa
(
72
%
,
p
=
0
.
02
;
and
31
%
,
p
=
0
.
001
)
.
Overexpression
of
Stat
3
and
p
-
Stat
3
positively
correlated
with
that
of
matrix
metalloproteinase-
2
(
MMP
2
)
,
a
known
regulator
for
cell
migration
,
in
65
%
of
ESCC
while
only
26
%
shown
in
benign
esophageal
mucosa
.
To
further
investigate
the
association
of
Stat
3
with
tumor
metastasis
in
vitro
,
invasion
of
EC
-
1
cells
(
a
human
ESCC
cell
line
)
were
investigated
with
Boyden
chambers
.
The
results
showed
that
transfection
of
Stat
3
not
only
promoted
invasion
of
EC
-
1
cells
but
also
significantly
induced
MMP
2
expression
in
a
dose-dependent
manner
.
In
contrast
,
suppressing
expression
of
endogenous
Stat
3
mRNA
and
protein
by
Stat
3
siRNA
significantly
reduced
EC
-
1
cell
invasion
and
MMP
2
expression
.
A
high
-affinity
Stat
3
-
binding
element
was
localized
to
the
positions
of
648
-
641
bp
(
TTCTCGAA
)
in
the
MMP
2
promoter
with
electrophoretic
mobility
shift
assay
.
Our
results
suggest
that
Stat
3
,
p
-
Stat
3
,
and
MMP
2
were
overexpressed
in
ESCC
and
associated
with
invasion
of
ESCC
;
and
Stat
3
up-regulated
expression
of
MMP
2
in
ESCC
through
directly
binding
to
the
MMP
2
promoter
.
Diseases
Validation
Diseases presenting
"squamous cell carcinoma"
symptom
carcinoma of the gallbladder
child syndrome
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
junctional epidermolysis bullosa
kallmann syndrome
kindler syndrome
liposarcoma
monosomy 21
oculocutaneous albinism
oral submucous fibrosis
papillon-lefèvre syndrome
This symptom has already been validated