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

被引：28
作者：
Adwan, H. [1 ]
Zhivkova-Galunska, M. [1 ]
Georges, R. [1 ]
Eyol, E. [1 ]
Kleeff, J. [2 ]
Giese, N. A. [3 ]
Friess, H. [2 ]
Bergmann, F. [4 ]
Berger, M. R. [1 ]
机构：
[1] Deutsch Krebsforschungszentrum, German Canc Res Ctr, Toxicol & Chemotherapy Unit, D-69120 Heidelberg, Germany
[2] Tech Univ Munich, Dept Gen Surg, Munich, Germany
[3] Univ Heidelberg, Dept Gen Surg, Heidelberg, Germany
[4] Univ Heidelberg, Inst Pathol, D-6900 Heidelberg, Germany
来源：
BRITISH JOURNAL OF CANCER | 2011年 / 105卷 / 02期
关键词：
HOXC8; pancreatic ductal adenocarcinoma; liver metastasis; osteopontin; osteonectin; HOMEOBOX GENE-EXPRESSION; HUMAN PROSTATE; CANCER CELLS; BONE SIALOPROTEIN; DIFFERENTIAL EXPRESSION; TARGET GENES; OSTEOPONTIN; SPARC; TUMOR; PROTEIN;
D O I：
10.1038/bjc.2011.217
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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. British Journal of Cancer (2011) 105, 288-295. doi: 10.1038/bjc.2011.217 www.bjcancer.com Published online 28 June 2011 (C) 2011 Cancer Research UK
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页码：288 / 295
页数：8
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