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International Journal of Hematology

, Volume 76, Issue 1, pp 50–54 | Cite as

Possible Attenuation of Fas-Mediated Signaling by Dominant Expression of Caspase-8 Aberrant Isoform in Adult T-cell Leukemia Cells

  • Kazuyuki Sugahara
  • Tomomi Hayashi
  • Natsuko Dateki
  • Yoichi Hirakata
  • Hitomi Harasawa
  • Masao Tomonaga
  • Yasuaki Yamada
  • Shimeru Kamihira
Review Article

Abstract

The Fas up-regulated in adult T-cell leukemia (ATL) cells is usually the wild-type protein and is usually functional, at least in vitro. However, primary ATL cells, in contrast to ATL cell lines, are not necessarily susceptible to anti-Fas—induced apoptosis. To clarify the mechanism tuning the apoptotic signal transduction initiated by the activation caspase-8 in ATL cells and ATL cell lines, we examined the expression profile of caspase-8, of which there are at least 8 isoforms at the messenger RNA (mRNA) level with the potential to finely tune the signal transduction. Reverse transcription polymerase chain reaction disclosed the 2 major mRNA bands of 815 bp (casp-8S) and 951 bp (casp-8L) with different expression profiles among normal CD4 T-cells, primary ATL cells, and ATL cell lines. Casp-8L was the predominant form in primary ATL cells, whereas casp-8S was predominant in ATL cell lines. Casp-8S was structurally intact as shown by nucleotide analysis, whereas casp-8L was shown to be generated by a 136-bp insertion between exons 8 and 9 and to carry a frame shift in the transcript, introducing a premature stop codon and probably resulting in a truncated protein of approximately 30 kd deduced for the casp-8L transcript.These results suggest that an imbalanced expression of casp-8 isoforms, especially the dominant casp-8L in primary ATL cells, is in part responsible for tumor pathology through the modulation of cell death via Fas-mediated signaling.

Key words

Caspase 8 Isoform ATL Apoptosis Fas/CD95 

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Copyright information

© The Japanese Society of Hematology 2002

Authors and Affiliations

  • Kazuyuki Sugahara
    • 1
  • Tomomi Hayashi
    • 1
  • Natsuko Dateki
    • 1
  • Yoichi Hirakata
    • 1
  • Hitomi Harasawa
    • 1
  • Masao Tomonaga
    • 2
  • Yasuaki Yamada
    • 1
  • Shimeru Kamihira
    • 1
  1. 1.Department of Laboratory MedicineNagasaki University Graduate School of Biomedical SciencesNagasaki CityJapan
  2. 2.Department of Hematology, Atomic Disease InstituteNagasaki University School of MedicineNagasakiJapan

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