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Loss of interleukin-2-dependency in HTLV-I-infected T cells on gene silencing of thioredoxin-binding protein-2

Oncogene volume 25, pages 2181–2191 (2006)Cite this article

Abstract

The transition from interleukin-2 (IL-2)-dependent to IL-2-independent growth is considered one of the key steps in the transformation of human T-cell leukemia virus type-I (HTLV-I)-infected T cells. The expression of thioredoxin-binding protein-2 (TBP-2) is lost during the transition of HTLV-I-infected T-cell lines. Here, we analysed the mechanism of loss of TBP-2 expression and the role of TBP-2 in IL-2-dependent growth in the in vitro model to investigate multistep transformation of HTLV-I. CpGs in the TBP-2 gene are methylated in IL-2-independent but not in IL-2-dependent cells. Sequential treatment with 5-aza-2′-deoxycytidine and a histone deacetylase inhibitor augmented histone acetylation and TBP-2 expression, suggesting that loss of TBP-2 expression is due to DNA methylation and histone deacetylation. In IL-2-dependent cells, a basal level of TBP-2 expression was maintained by IL-2 associated with cellular growth, whereas TBP-2 expression was upregulated on deprivation of IL-2 associated with growth suppression. Overexpression of TBP-2 in IL-2-independent cells suppressed the growth and partially restored responsiveness to IL-2. Knockdown of TBP-2 caused the IL-2-dependent cells to show partial growth without IL-2. These results suggested that epigenetic silencing of the TBP-2 gene results in a loss of responsiveness to IL-2, contributing to uncontrolled IL-2-independent growth in HTLV-I-infected T-cell lines.

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References

  • Butler LM, Zhou X, Xu WS, Scher HI, Rifkind RA, Marks PA et al. (2002). Proc Natl Acad Sci USA 99: 11700–11705.

  • Cameron EE, Bachman KE, Myohanen S, Herman JG, Baylin SB . (1999). Nat Genet 21: 103–107.

  • Chen KS, DeLuca HF . (1994). Biochim Biophys Acta 1219: 26–32.

  • Coombes MM, Briggs KL, Bone JR, Clayman GL, El-Naggar AK, Dent SY . (2003). Oncogene 22: 8902–8911.

  • Gardiner-Garden M, Frommer M . (1987). J Mol Biol 196: 261–282.

  • Goldberg SF, Miele ME, Hatta N, Takata M, Paquette-Straub C, Freedman LP et al. (2003). Cancer Res 63: 432–440.

  • Han SH, Jeon JH, Ju HR, Jung U, Kim KY, Yoo HS et al. (2003). Oncogene 22: 4035–4046.

  • Holmgren A . (1985). Annu Rev Biochem 54: 237–271.

  • Jeang KT, Giam C, Majone F, Aboud M . (2004). J Biol Chem 279: 31991–31994.

  • Maeda M, Shimizu A, Ikuta K, Okamoto H, Kashihara M, Uchiyama T et al. (1985). J Exp Med 162: 2169–2174.

  • Maeda M . (1992). Hum Cell 5: 70–78.

  • Makino S, Masutani H, Maekawa N, Konishi I, Fujii S, Yamamoto R et al. (1992). Immunology 76: 578–583.

  • Masutani H, Yodoi J . (2002). Methods Enzymol 347: 279–286.

  • Matsuoka M . (2003). Oncogene 22: 5131–5140.

  • Migone TS, Lin JX, Cereseto A, Mulloy JC, O'Shea JJ, Franchini G et al. (1995). Science 269: 79–81.

  • Morgan DA, Ruscetti FW, Gallo R . (1976). Science 193: 1007–1008.

  • Nishinaka Y, Nishiyama A, Masutani H, Oka S, Ahsan MK, Nakayama Y et al. (2004a). Cancer Res 64: 1287–1292.

  • Nishinaka Y, Masutani H, Oka S, Matsuo Y, Yamaguchi Y, Nishio K et al. (2004b). J Biol Chem 279: 37559–37565.

  • Nishiyama A, Matsui M, Iwata S, Hirota K, Masutani H, Nakamura H et al. (1999). J Biol Chem 274: 21645–21650.

  • Nosaka K, Maeda M, Tamiya S, Sakai T, Mitsuya H, Matsuoka M . (2000). Cancer Res 60: 1043–1048.

  • Okamoto T, Ohno Y, Tsugane S, Watanabe S, Shimoyama M, Tajima K et al (1989). Jpn J Cancer Res 80: 191–195.

  • Satoh A, Toyota M, Itoh F, Sasaki Y, Suzuki H, Ogi K et al. (2003). Cancer Res 63: 8606–8613.

  • Spencer VA, Sun JM, Li L, Davie JR . (2003). Methods 31: 67–75.

  • Tagaya Y, Maeda Y, Mitsui A, Kondo N, Matsui H, Hamuro J et al. (1989). EMBO J 13: 2244.

  • Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H . (1977). Blood 50: 481–492.

  • Ushijima T, Okochi-Takada E . (2005). Cancer Sci 96: 206–211.

  • Yasunaga J, Taniguchi Y, Nosaka K, Yoshida M, Satou Y, Sakai T et al. (2004). Cancer Res 64: 6002–6009.

  • Yodoi J, Takatsuki K, Masuda T . (1974). New Engl J Med 290: 572–573.

  • Yoshida M, Miyoshi I, Hinuma Y . (1982). Proc Natl Acad Sci USA 79: 2031–2035.

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Acknowledgements

We thank Dr Koichi Ikuta for discussions, and Ms Yoko Kanekiyo and Ms Satoko Maeji for secretarial assistance. This work was supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Research and Development Program for New Bio-Industry Initiatives.

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Authors and Affiliations

  1. Department of Biological Responses, Institute for Virus Research, Kyoto University, Shogoin, Kawahara-cho, Sakyo-ku, Kyoto, Japan

    M K Ahsan, H Masutani, Y Yamaguchi, Y-C Kim, Y Nishinaka, M Maeda & J Yodoi

  2. Research Center for Acquired Immunodeficiency Syndrome, Institute for Virus Research, Kyoto University, Shogoin, Kawahara-cho, Sakyo-ku, Kyoto, Japan

    K Nosaka & M Matsuoka

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  1. M K Ahsan
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Correspondence to H Masutani.

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Ahsan, M., Masutani, H., Yamaguchi, Y. et al. Loss of interleukin-2-dependency in HTLV-I-infected T cells on gene silencing of thioredoxin-binding protein-2. Oncogene 25, 2181–2191 (2006). https://doi.org/10.1038/sj.onc.1209256

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