18 - World Journal of Gastroenterology

2618 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol May 14, 2007 Volume 13 Number 18
in rat pancreatectomy model and PDX-1 was re-activated
in the ductal cells, thereby suggesting that re-activation of
PDX-1 is a marker of pancreatic stem cells.
There is overwhelming evidence that cancer stem
cells, which are considered to originate from somatic stem
cells, should be responsible for tumors malignancy [17] .
Miyamoto et al [9] found that signal molecules that regulate
proliferation and differentiation of embryonic stem cell
were activated in human pancreatic cancers. Thus, we
deduced that PDX-1 may be re-activated in the process of
transformation from pancreatic stem cells to pancreatic
cancer stem cells.
To investigate whether PDX-1 was re-expressed
in pancreatic cancer and its role in pancreatic cancer
development, we detected PDX-1 protein and mRNA
expression in 56 pancreatic cancer tissues. To validate
the used methods, we also analyzed normal human
pancreatic tissues. Results of immunohistochemistry
indicated that PDX-1 was only weekly expressed in beta
cells of the pancreatic islet in normal pancreatic tissues,
which is in agreement with previous studies in mice and
human pancreas [11,12] , but PDX-1 was re-activated in
pancreatic cancers. About 41.1% samples showed positive
immunostaining for PDX-1 in the cytoplasm and nuclei
of cells, especially in the cells located at the leading edge
of infiltration, thereby implying that PDX-1 plays a role in
pancreatic cancer infiltration. Results of Western blot were
in consonance with that of immunohistochemistry. In
addition, we analyzed the correlation of PDX-1 expression
with tumor characteristics. We found that lymph node
metastasis, TNM grading and pathological grading were all
significantly correlated with PDX-1 expression.
To study the correlation of PDX-1 expression with
cell proliferation, we detected the expression of PCNA in
pancreatic cancer by immunohistochemistry. The positive
rate of PCNA in PDX-1-positive samples was as high as
78.2%, whereas that in PDX-1-negative samples was only
36.4%, suggesting that PDX-1-positive cells had higher
potential of proliferation. Many studies have demonstrated
high frequency of mutations of oncogene such as K-ras
and tumor suppressor genes such as p16, p53 in pancreatic
cancer tissues and cell lines [8,18,19] . Based on our study, we
deduced that the alteration of PDX-1 expression might
represent one of those genetic changes.
In summary, PDX-1 is re-expressed in pancreatic
cancers, and its expression level has a significant correlation
with pathological grading, TNM grading, tumor metastasis
and tumor cell proliferation. Since PDX-1 is considered a
marker of pancreatic stem cells, we tentatively put forward
that cells that express PDX-1 in pancreatic cancers may be
cancer stem cells. How does the PDX-1 molecule affect
the malignancy of a particular cell is awaited to be studied
in our future work.
ACKNOWLEDGMENTS
The authors are grateful to the technical assistance from
Yuan Tian and Jin-Hui Zhang, the Research Laboratory of
www.wjgnet.com
General Surgery, Union Hospital, Wuhan.
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S- Editor Liu Y L- Editor Kumar M E- Editor Wang HF