Expression of HOXC8 is inversely related to the progression and metastasis of pancreatic ductal adenocarcinoma

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...

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Hauptverfasser: Adwan, Hassan (VerfasserIn) , Zhivkova-Galunska, M. (VerfasserIn) , Georges, R. (VerfasserIn) , Eyol, E. (VerfasserIn) , Kleeff, J. (VerfasserIn) , Giese, Nathalia (VerfasserIn) , Friess, H. (VerfasserIn) , Bergmann, Frank (VerfasserIn) , Berger, M. R. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 28 June 2011
In: British journal of cancer
Year: 2011, Jahrgang: 105, Heft: 2, Pages: 288-295
ISSN:1532-1827
DOI:10.1038/bjc.2011.217
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/bjc.2011.217
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/bjc2011217
Volltext
Verfasserangaben:H. Adwan, M. Zhivkova-Galunska, R. Georges, E. Eyol, J. Kleeff, N.A. Giese, H. Friess, F. Bergmann and M.R. Berger

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520 |a 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. 
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