Publication: Nuclear accumulation of glioma-associated oncogene 2 protein and enhanced expression of forkhead-box transcription factor M1 protein in human hepatocellular carcinoma
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Date
2010
Authors
Lin, M. ; Guo, Lankai ; Liu, H. ; Du, J. ; Yang, Jilong ; Zhang, L.J. ; Zhang, B.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The hedgehog (Hh) signaling pathway has
been reported to be crucial in human carcinogenesis and
tumor progression. Glioma-associated oncogenes (Gli),
are zinc finger transcription factors which mediate the
transcriptional response to Hh signaling. To explore the
role of Gli in the development and progression of
hepatocellular carcinoma (HCC), we investigated the
expression of Gli2 and FoxM1 (forkhead-box
transcription factor M1) which is one of the Gli
downstream target genes modulating cell cycle
progression in 91 specimens of human HCCs with
immunohistochemistry. These immunostaining results
were compared with various clinicopathologic
parameters. Immunoreactivity of Gli2 and FoxM1 was
observed respectively in 84.6% (77/91) and 80.2%
(73/91) cases of HCC tumor tissues, and this was
considerably higher than expression in the peritumoral
tissues. Distribution of Gli2 and FoxM1 proteins in
tumor cells was nuclear with or without cytoplasmic
staining, or cytoplasmic alone. Statistically, increased
nuclear immunopositivity of Gli2 protein correlated
significantly with poorer tumor differentiation (P<0.05),
as well as with portal vein tumor thrombosis (P<0.05).
In addition, overexpression of FoxM1 protein was
significantly associated with increased tumor grade
(P<0.01) and advanced tumor stage (P<0.05). Moreover,
there was a significant association between the
expressions of Gli2 and FoxM1 proteins in HCC
(r=0.464, P=0.000). This is consistent with the concept
that in human HCC, the Hh signaling pathway is
involved in the differentiation and proliferation of tumor cells, in part through inducing nuclear accumulation of
Gli2 protein and subsequent upregulation of FoxM1
protein.
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