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Aberrant calreticulin expression is involved in the dedifferentiation of dedifferentiated liposarcoma.
[dedifferentiated liposarcoma]
Liposarcomas
are
a
representative
group
of
soft
tissue
sarcomas
with
variably
hampered
adipogenesis
,
which
is
most
exemplified
by
its
dedifferentiated
subtype
.
However
,
the
factor
(
s
)
responsible
for
inhibiting
adipocyte
differentiation
remains
unknown
.
A
recent
gene
expression
profiling
study
identified
several
unique
genes
that
were
highly
expressed
in
dedifferentiated
liposarcoma
,
and
the
gene
encoding
calreticulin
(
CALR
)
,
a
major
Ca
(
2
+
)
-
buffering
protein
that
can
inhibit
adipocyte
differentiation
,
was
found
to
be
overexpressed
.
Thus
,
we
investigated
the
expression
of
calreticulin
in
45
cases
of
liposarcomas
,
including
15
dedifferentiated
tumors
,
at
both
the
protein
and
mRNA
levels
.
Immunohistochemically
,
calreticulin
was
consistently
expressed
in
the
dedifferentiated
areas
of
dedifferentiated
liposarcomas
and
commonly
observed
in
atypical
stromal
cells
and
/
or
lipoblasts
in
the
well-differentiated
areas
(
87
%
)
,
whereas
large
vacuolated
adipocytic
cells
in
either
the
tumors
or
normal
fat
were
essentially
negative
.
These
results
were
further
supported
by
the
findings
of
Western
blot
and
quantitative
RT-PCR
analyses
.
Although
abnormalities
in
19
p
13
.
1
-
13
.
2
where
CALR
is
localized
were
uncommon
in
the
dedifferentiated
liposarcomas
examined
by
fluorescence
in
situ
hybridization
,
expression
of
miR-
1257
,
a
putative
microRNA
that
targets
calreticulin
,
was
suppressed
in
the
dedifferentiated
subtype
.
The
down-regulation
of
calreticulin
by
small
-interfering
RNA
could
induce
adipogenesis
in
dedifferentiated
liposarcoma
cells
and
reduce
cell
proliferation
.
Our
results
therefore
suggest
that
aberrantly
expressed
calreticulin
in
dedifferentiated
liposarcoma
is
involved
in
its
dedifferenitation
and
/
or
tumor
progression
.
Diseases
Validation
Diseases presenting
"and the gene encoding calreticulin"
symptom
dedifferentiated liposarcoma
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