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Over-expressed Fas improves the apoptosis of malignant T-cells in vitro and vivo

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Abstract

Fas play a critical role in T-cell apoptosis by functioning as a major cell-surface death receptor. To explore a potential method that can improve the sensitivity to Fas-mediated apoptosis in malignant precursor T-cells. Fas gene was stable transfected into Jurkat cells to establish a new cell line named Jurkat-Fas with over-expressed Fas. RT-PCR, real-time RT-PCR, flow cytometry, and confocal microscopy assay were performed to detect the Fas level of mRNA and protein in the two cell lines. The sensitivities to Fas-mediated apoptosis of the two cell lines were evaluated by flow cytometry with Alexa Fluor 488 annexin V/PI staining in vitro. Tumor xenograft models were prepared with Jurkat and Jurkat-Fas cells for in vivo study. Fas mRNA and protein levels in Jurkat-Fas cell line were higher than that in Jurkat cell line. Compared to Jurkat cells, apoptosis rates of Jurkat-Fas cells were remarkably higher in vitro, and the tumor growth of Jurkat-Fas cells in nude mice was significantly inhibited in vivo. Stable over-expression of extrinsic Fas gene can significantly ameliorate the sensitivity to Fas-mediated apoptosis in human malignant T-cell, which indicates a novel strategy to improve therapeutic effects on precursor T-cell malignancy.

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References

  1. Hoelzer D, Gokbuget N (2009) T-cell lymphoblastic lymphoma and T-cell acute lymphoblastic leukemia: a separate entity? Clin Lymphoma Myeloma 9(Suppl 3):S214–S221

    PubMed  Google Scholar 

  2. Brunner T, Mogil RJ, LaFace D et al (1995) Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature 373:441–444

    Article  PubMed  CAS  Google Scholar 

  3. Jones CL, Wain EM, Chu CC et al (2010) Downregulation of Fas gene expression in Sezary syndrome is associated with promoter hypermethylation. J Invest Dermatol 130:1116–1125

    Article  PubMed  CAS  Google Scholar 

  4. van Doorn R, Dijkman R, Vermeer MH et al (2002) A novel splice variant of the Fas gene in patients with cutaneous T-cell lymphoma. Cancer Res 62:5389–5392

    PubMed  Google Scholar 

  5. Shen L, Liang AC, Lu L et al (2002) Frequent deletion of Fas gene sequences encoding death and transmembrane domains in nasal natural killer/T-cell lymphoma. Am J Pathol 161:2123–2131

    Article  PubMed  CAS  Google Scholar 

  6. Takakuwa T, Dong Z, Takayama H et al (2001) Frequent mutations of Fas gene in thyroid lymphoma. Cancer Res 61:1382–1385

    PubMed  CAS  Google Scholar 

  7. Dereure O, Levi E, Vonderheid EC et al (2002) Infrequent Fas mutations but no Bax or p53 mutations in early mycosis fungoides: a possible mechanism for the accumulation of malignant T lymphocytes in the skin. J Invest Dermatol 118:949–956

    Article  PubMed  CAS  Google Scholar 

  8. Takakuwa T, Dong Z, Nakatsuka S et al (2002) Frequent mutations of Fas gene in nasal NK/T cell lymphoma. Oncogene 21:4702–4705

    Article  PubMed  CAS  Google Scholar 

  9. Osella-Abate S, Zaccagna A, Savoia P et al (2001) Expression of apoptosis markers on peripheral blood lymphocytes from patients with cutaneous T-cell lymphoma during extracorporeal photochemotherapy. J Am Acad Dermatol 44:40–47

    Article  PubMed  CAS  Google Scholar 

  10. Wu J, Nihal M, Siddiqui J et al (2009) Low FAS/CD95 expression by CTCL correlates with reduced sensitivity to apoptosis that can be restored by FAS upregulation. J Invest Dermatol 129:1165–1173

    Article  PubMed  CAS  Google Scholar 

  11. Contassot E, Kerl K, Roques S et al (2008) Resistance to FasL and tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in Sezary syndrome T-cells associated with impaired death receptor and FLICE-inhibitory protein expression. Blood 111:4780–4787

    Article  PubMed  CAS  Google Scholar 

  12. Maeda T, Nakayama S, Yamada Y et al (2002) The conformational alteration of the mutated extracellular domain of Fas in an adult T-cell leukemia cell line. Biochem Biophys Res Commun 296:1251–1256

    Article  PubMed  CAS  Google Scholar 

  13. Beltinger C, Kurz E, Bohler T et al (1998) CD95 (APO-1/Fas) mutations in childhood T-lineage acute lymphoblastic leukemia. Blood 91:3943–3951

    PubMed  CAS  Google Scholar 

  14. Tamiya S, Etoh K, Suzushima H et al (1998) Mutation of CD95 (Fas/Apo-1) gene in adult T-cell leukemia cells. Blood 91:3935–3942

    PubMed  CAS  Google Scholar 

  15. Tawara M, Maeda T, Yamada Y et al (2003) Aberrant processing of Fas transcripts in adult T-cell leukemia: a possible role in tumor cell survival. Cancer Lett 193:235–242

    Article  PubMed  CAS  Google Scholar 

  16. Wohlfart S, Sebinger D, Gruber P et al (2004) FAS (CD95) mutations are rare in gastric MALT lymphoma but occur more frequently in primary gastric diffuse large B-cell lymphoma. Am J Pathol 164:1081–1089

    Article  PubMed  CAS  Google Scholar 

  17. Weller M, Malipiero U, Rensing-Ehl A et al (1995) Fas/APO-1 gene transfer for human malignant glioma. Cancer Res 55:2936–2944

    PubMed  CAS  Google Scholar 

  18. Coleman CN, Cohen JR, Burke JS et al (1981) Lymphoblastic lymphoma in adults: results of a pilot protocol. Blood 57:679–684

    PubMed  CAS  Google Scholar 

  19. Coleman CN, Picozzi VJ Jr, Cox RS et al (1986) Treatment of lymphoblastic lymphoma in adults. J Clin Oncol 4:1628–1637

    PubMed  CAS  Google Scholar 

  20. Colgan JP, Andersen J, Habermann TM et al (1994) Long-term follow-up of a CHOP-based regimen with maintenance therapy and central nervous system prophylaxis in lymphoblastic non-Hodgkin’s lymphoma. Leuk Lymphoma 15:291–296

    Article  PubMed  CAS  Google Scholar 

  21. Chen YC, Ho CL, Kao WY et al (2001) Adult lymphoblastic lymphoma in Taiwan: an analysis of treatment results of 26 patients. Ann Hematol 80:647–652

    Article  PubMed  CAS  Google Scholar 

  22. Burkhardt B, Reiter A, Landmann E et al (2009) Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: a report from the berlin-frankfurt-muenster group. J Clin Oncol 27:3363–3369

    Article  PubMed  Google Scholar 

  23. Debatin KM, Krammer PH (2004) Death receptors in chemotherapy and cancer. Oncogene 23:2950–2966

    Article  PubMed  CAS  Google Scholar 

  24. Ashkenazi A, Herbst RS (2008) To kill a tumor cell: the potential of proapoptotic receptor agonists. J Clin Invest 118:1979–1990

    Article  PubMed  CAS  Google Scholar 

  25. Ghobrial IM, Witzig TE, Adjei AA (2005) Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin 55:178–194

    Article  PubMed  Google Scholar 

  26. Zapata JM, Pawlowski K, Haas E et al (2001) A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains. J Biol Chem 276:24242–24252

    Article  PubMed  CAS  Google Scholar 

  27. Krammer PH (2000) CD95’s deadly mission in the immune system. Nature 407:789–795

    Article  PubMed  CAS  Google Scholar 

  28. Meech SJ, Edelson R, Walsh P et al (2001) Reversible resistance to apoptosis in cutaneous T-cell lymphoma. Ann NY Acad Sci 941:46–58

    Article  PubMed  CAS  Google Scholar 

  29. Ni X, Zhang C, Talpur R et al (2005) Resistance to activation-induced cell death and bystander cytotoxicity via the Fas/Fas ligand pathway are implicated in the pathogenesis of cutaneous T-cell lymphomas. J Invest Dermatol 124:741–750

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, No 188 Shizi Street, Suzhou, 215006, China

    Linghao Li, Ri Zhang, Zixing Chen, Shengli Xue, Xiuli Wang & Changgeng Ruan

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  1. Linghao Li
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  2. Ri Zhang
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  3. Zixing Chen
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  4. Shengli Xue
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  5. Xiuli Wang
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  6. Changgeng Ruan
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Correspondence to Ri Zhang.

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Li, L., Zhang, R., Chen, Z. et al. Over-expressed Fas improves the apoptosis of malignant T-cells in vitro and vivo. Mol Biol Rep 38, 5371–5377 (2011). https://doi.org/10.1007/s11033-011-0689-2

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  • DOI: https://doi.org/10.1007/s11033-011-0689-2

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