TY - JOUR
T1 - Expression of HOXC8 is inversely related to the progression and metastasis of pancreatic ductal adenocarcinoma
AU - Adwan, H.
AU - Zhivkova-Galunska, M.
AU - Georges, R.
AU - Eyol, E.
AU - Kleeff, J.
AU - Giese, N. A.
AU - Friess, H.
AU - Bergmann, F.
AU - Berger, M. R.
PY - 2011/7/12
Y1 - 2011/7/12
N2 - Background:The transcription factor HOXC8 regulates many genes involved in tumour progression. This study was to investigate the role of HOXC8 in pancreatic ductal adenocarcinoma (PDAC) growth and metastasis.Methods:The Hoxc8 expression was determined in 15 PDAC cell lines and human specimens by RT-polymerase chain reaction and/or immunohistochemistry. The effects of HOXC8 silencing by RNA interference were investigated by functional tests.Results:The Hoxc8 mRNA expression in PDAC cell lines was negatively related to their growth in vivo. Except for Suit2-007 cells, only those with low Hoxc8 mRNA expression grew in nude rats. Successful down-regulation of HOXC8 expression caused increased proliferation, migration (P=0.05) and colony formation (P=0.05) in Suit2-007, Panc-1 and MIA PaCa-2 PDAC cells, respectively. The Hoxc8 mRNA levels in diseased human pancreas tissues were significantly increased over normal in PDAC and autoimmune chronic pancreatitis specimens (P=0.01, respectively), but negatively related to tumour stage (P=0.09). In primary and metastatic tumour samples, immunohistochemical staining for HOXC8 was stronger in surrounding than in neoplastic tissues. Furthermore, grading of primary carcinomas was negatively associated with HOXC8 staining (P=0.03). Liver metastases showed the lowest HOXC8 expression of all neoplastic lesions.Conclusion:These data indicate that HOXC8 expression is inversely related to PDAC progression and metastasis.
AB - Background:The transcription factor HOXC8 regulates many genes involved in tumour progression. This study was to investigate the role of HOXC8 in pancreatic ductal adenocarcinoma (PDAC) growth and metastasis.Methods:The Hoxc8 expression was determined in 15 PDAC cell lines and human specimens by RT-polymerase chain reaction and/or immunohistochemistry. The effects of HOXC8 silencing by RNA interference were investigated by functional tests.Results:The Hoxc8 mRNA expression in PDAC cell lines was negatively related to their growth in vivo. Except for Suit2-007 cells, only those with low Hoxc8 mRNA expression grew in nude rats. Successful down-regulation of HOXC8 expression caused increased proliferation, migration (P=0.05) and colony formation (P=0.05) in Suit2-007, Panc-1 and MIA PaCa-2 PDAC cells, respectively. The Hoxc8 mRNA levels in diseased human pancreas tissues were significantly increased over normal in PDAC and autoimmune chronic pancreatitis specimens (P=0.01, respectively), but negatively related to tumour stage (P=0.09). In primary and metastatic tumour samples, immunohistochemical staining for HOXC8 was stronger in surrounding than in neoplastic tissues. Furthermore, grading of primary carcinomas was negatively associated with HOXC8 staining (P=0.03). Liver metastases showed the lowest HOXC8 expression of all neoplastic lesions.Conclusion:These data indicate that HOXC8 expression is inversely related to PDAC progression and metastasis.
KW - HOXC8
KW - liver metastasis
KW - osteonectin
KW - osteopontin
KW - pancreatic ductal adenocarcinoma
UR - http://www.scopus.com/inward/record.url?scp=79960222639&partnerID=8YFLogxK
U2 - 10.1038/bjc.2011.217
DO - 10.1038/bjc.2011.217
M3 - Article
C2 - 21712827
AN - SCOPUS:79960222639
SN - 0007-0920
VL - 105
SP - 288
EP - 295
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 2
ER -
