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Proinflammatory cytokines cause FAT10 upregulation in cancers of liver and colon

Oncogene volume 27, pages 6068–6074 (2008)Cite this article

Abstract

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)-γ and tumor necrosis factor (TNF)-α 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-γ- and TNF-α-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.

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Acknowledgements

We thank Klaus Scherrer for the contribution of the iota antibody and Gerardo Alvarez for excellent technical assistance. Darius Moradpour is acknowledged for the contribution of HCC cell lines. This work was supported from the grants Az 10.05.1.145 and Az 10.06.2.183 of the Fritz Thyssen Foundation.

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Authors and Affiliations

  1. Department of Biology, Division of Immunology, University of Constance, Konstanz, Germany

    S Lukasiak, P Oehlschlaeger, G Schmidtke & M Groettrup

  2. Institute of Pathology, University Hospital, University of Heidelberg, Heidelberg, Germany

    C Schiller, F Autschbach, P Schirmacher & K Breuhahn

  3. Biotechnology Institute Thurgau at the University of Konstanz, Kreuzlingen, Switzerland

    P Krause, D F Legler & M Groettrup

Authors
  1. S Lukasiak
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  2. C Schiller
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  3. P Oehlschlaeger
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  4. G Schmidtke
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  5. P Krause
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  6. D F Legler
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  7. F Autschbach
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  8. P Schirmacher
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  9. K Breuhahn
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  10. M Groettrup
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Corresponding author

Correspondence to M Groettrup.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Lukasiak, S., Schiller, C., Oehlschlaeger, P. et al. Proinflammatory cytokines cause FAT10 upregulation in cancers of liver and colon. Oncogene 27, 6068–6074 (2008). https://doi.org/10.1038/onc.2008.201

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  • DOI: https://doi.org/10.1038/onc.2008.201

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