Proinflammatory cytokines cause FAT10 upregulation in cancers of liver and colon

被引:133
作者
Lukasiak, S. [1 ]
Schiller, C. [2 ]
Oehlschlaeger, P. [1 ]
Schmidtke, G. [1 ]
Krause, P. [3 ]
Legler, D. F. [3 ]
Autschbach, F. [2 ]
Schirmacher, P. [2 ]
Breuhahn, K. [2 ]
Groettrup, M. [1 ,3 ]
机构
[1] Univ Constance, Div Immunol, Dept Biol, D-78457 Constance, Germany
[2] Univ Heidelberg, Inst Pathol, Univ Heidelberg Hosp, D-6900 Heidelberg, Germany
[3] Univ Konstanz, Biotechnol Inst Thurgau, Kreuzlingen, Switzerland
关键词
FAT10; ubiquitin-like modifiers; hepatocellular carcinoma; colon carcinoma; interferon-gamma;
D O I
10.1038/onc.2008.201
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mRNA of the ubiquitin-like modifier FAT10 has been reported to be overexpressed in 90% of hepatocellular carcinoma (HCC) and in over 80% of colon, ovary and uterus carcinomas. Elevated FAT10 expression in malignancies was attributed to transcriptional upregulation upon the loss of p53. Moreover, FAT10 induced chromosome instability in long-term in vitro culture, which led to the hypothesis that FAT10 might be involved in carcinogenesis. In this study we show that interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha synergistically upregulated FAT10 expression in liver and colon cancer cells 10- to 100-fold. Real-time RT-PCR revealed that FAT10 mRNA was significantly overexpressed in 37 of 51 (72%) of human HCC samples and in 8 of 15 (53%) of human colon carcinomas. The FAT10 cDNA sequences in HCC samples were not mutated and intact FAT10 protein was detectable. FAT10 expression in both cancer tissues correlated with expression of the IFN-gamma- and TNF-alpha-dependent proteasome subunit LMP2 strongly suggesting that proinflammatory cytokines caused the joint overexpression of FAT10 and LMP2. NIH3T3 transformation assays revealed that FAT10 had no transforming capability. Taken together, FAT10 qualifies as a marker for an interferon response in HCC and colon carcinoma but is not significantly overexpressed in cancers lacking a proinflammatory environment.
引用
收藏
页码:6068 / 6074
页数:7
相关论文
共 22 条
[1]   Identification and analysis of a novel member of the ubiquitin family expressed in dendritic cells and mature B cells [J].
Bates, EFM ;
Ravel, O ;
Dieu, MC ;
Ho, S ;
Guret, C ;
Bridon, JM ;
AitYahia, S ;
Briere, F ;
Caux, C ;
Banchereau, J ;
Lebecque, S .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (10) :2471-2477
[2]   Molecular profiling of human hepatocellular carcinoma defines mutually exclusive interferon regulation and insulin-like growth factor II overexpression [J].
Breuhahn, K ;
Vreden, S ;
Haddad, R ;
Beckebaum, S ;
Stippel, D ;
Flemming, P ;
Nussbaum, T ;
Caselmann, WH ;
Haab, BB ;
Schirmacher, P .
CANCER RESEARCH, 2004, 64 (17) :6058-6064
[3]   FAT10/diubiquitin-like protein-deficient mice exhibit minimal phenotypic differences [J].
Canaan, Allon ;
Yu, Xiaofeng ;
Booth, Carmen J. ;
Lian, Jin ;
Lazar, Isaac ;
Gamfi, Serwa L. ;
Castille, Katrina ;
Kohya, Naohiko ;
Nakayama, Yasuhiro ;
Liu, Yuan-Ching ;
Eynon, Elizabeth ;
Flavell, Richard ;
Weissman, Sherman M. .
MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (13) :5180-5189
[4]   E1-L2 activates both ubiquitin and FAT10 [J].
Chiu, Yu-Hsin ;
Sun, Qinmiao ;
Chen, Zhijian J. .
MOLECULAR CELL, 2007, 27 (06) :1014-1023
[5]   Identification of seven new human MHC class I region genes around the HLA-F locus [J].
Fan, WF ;
Cai, WW ;
Parimoo, S ;
Lennon, GG ;
Weissman, SM .
IMMUNOGENETICS, 1996, 44 (02) :97-103
[6]   FAT10, a ubiquitin-independent signal for proteasomal degradation [J].
Hipp, MS ;
Kalveram, B ;
Raasi, S ;
Groettrup, M ;
Schmidtke, G .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (09) :3483-3491
[7]   NEDD8 ultimate Buster-1L interacts with the ubiquitin-like protein FAT10 and accelerates its degradation [J].
Hipp, MS ;
Raasi, S ;
Groettrup, M ;
Schmidtke, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (16) :16503-16510
[8]   Molecular pathogenesis of human hepatocellular carcinoma [J].
Kern, MA ;
Breuhahn, K ;
Schirmacher, P .
ADVANCES IN CANCER RESEARCH, VOL 86, 2002, 86 :67-112
[9]   Immunoproteasomes largely replace constitutive proteasomes during an antiviral and antibacterial immune response in the liver [J].
Khan, S ;
van den Broek, M ;
Schwarz, K ;
de Giuli, R ;
Diener, PA ;
Groettrup, M .
JOURNAL OF IMMUNOLOGY, 2001, 167 (12) :6859-6868
[10]   Expression of the FAT 10 gene is highly upregulated in hepatocellular carcinoma and other gastrointestinal and gynecological cancers [J].
Lee, CGL ;
Ren, JW ;
Cheong, ISY ;
Ban, KHK ;
Ooi, LLPJ ;
Tan, SY ;
Kan, A ;
Nuchprayoon, I ;
Jin, RX ;
Lee, KH ;
Choti, M ;
Lee, LA .
ONCOGENE, 2003, 22 (17) :2592-2603