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

被引:29
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
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
引用
收藏
页码:288 / 295
页数:8
相关论文
共 40 条
[1]   Deregulated homeobox gene expression in cancer: Cause or consequence? [J].
Abate-Shen, C .
NATURE REVIEWS CANCER, 2002, 2 (10) :777-785
[2]   Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells [J].
Adwan, H ;
Bäuerle, TJ ;
Berger, MR .
CANCER GENE THERAPY, 2004, 11 (02) :109-120
[3]  
Agrawal D, 2002, J NATL CANCER I, V94, P513
[4]   HOXC8 Inhibits Androgen Receptor Signaling in Human Prostate Cancer Cells by Inhibiting SRC-3 Recruitment to Direct Androgen Target Genes [J].
Axlund, Sunshine Daddario ;
Lambert, James R. ;
Nordeen, Steven K. .
MOLECULAR CANCER RESEARCH, 2010, 8 (12) :1643-1655
[5]  
Belting HG, 1998, J EXP ZOOL, V282, P196, DOI 10.1002/(SICI)1097-010X(199809/10)282:1/2<196::AID-JEZ22>3.0.CO
[6]  
2-R
[7]  
Brekken Rolf A., 2001, Matrix Biology, V19, P816
[8]  
BROWN LF, 1994, AM J PATHOL, V145, P610
[9]  
Chen KN, 2005, CLIN CANCER RES, V11, P1044
[10]   Homeobox genes in normal and malignant cells [J].
Cillo, C ;
Cantile, M ;
Faiella, A ;
Boncinelli, E .
JOURNAL OF CELLULAR PHYSIOLOGY, 2001, 188 (02) :161-169