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CBX8, a novel DNA repair protein, promotes tumorigenesis in human esophageal carcinoma.
[esophageal carcinoma]
DNA
damage
response
and
repair
are
carried
out
by
certain
proteins
following
damage
by
environmental
clastogens
,
such
as
ionizing
radiation
and
reactive
oxygen
species
.
It
has
been
reported
that
many
carcinomas
that
are
characterized
by
resistance
to
chemotherapy
and
poor
outcomes
show
dysfunction
of
these
proteins
.
Chromobox
homologue
8
(
CBX
8
)
,
a
member
of
the
polycomb
group
of
proteins
,
has
been
identified
as
a
factor
that
protects
tumor
cells
from
the
detrimental
effects
of
ionizing
radiation
(
IR
)
or
hydrogen
peroxide
(
H
2
O
2
)
.
In
this
study
,
we
found
that
CBX
8
was
up-regulated
in
esophageal
carcinoma
tissues
compared
with
adjacent
non-cancerous
tissues
(
P
<
0
.
01
)
and
correlated
with
TNM
stage
in
esophageal
squamous
cell
carcinoma
patients
.
Depletion
of
CBX
8
decreased
cell
proliferation
both
in
vitro
and
in
vivo
and
increased
the
phosphorylation
levels
of
p
21
,
Wee
1
,
and
CHK
1
,
which
result
in
cyclin-dependent
kinase
inhibition
and
cell-cycle
delay
.
CBX
8
depletion
also
led
to
accumulation
of
spontaneous
DNA
damage
and
raised
the
sensitivity
of
tumor
cells
to
IR
or
H
2
O
2
.
We
also
found
that
the
total
level
of
CBX
8
in
the
cells
was
increased
after
treating
tumor
cells
with
clastogens
.
In
addition
,
our
data
showed
that
decreased
CBX
8
expression
was
accompanied
by
the
reduction
of
EZH
2
and
EED
,
which
have
been
reported
to
participate
in
DNA
damage
repair
.
Collectively
,
CBX
8
might
emerge
as
an
oncogene
for
promoting
the
proliferation
of
tumor
cells
and
raising
the
resistance
of
neoplasms
to
chemotherapy
.
Diseases
Validation
Diseases presenting
"cyclin-dependent kinase inhibition"
symptom
esophageal carcinoma
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