| Research Abstract |
Tumor is an imbalance in the cell number between cell-division and cell-death. A signal of apoptotic cell-death is triggered by Fas, which is a major death receptor belonging to a TNFR superfamily and is well known to be up-regulated in ATL cells.
To address the relationship between molecular pathology of tumor and aberrant Fas expression, we studied Fas gene and its proteins of isoforms in ATL cells and could demonstrated the following results. Firstly, ATL cells, of which membrane-Fas (mFas) are up-regulated in about 90% of ATL cases, were demonstared to prevent from apoptotic cell death by means of decoy function of hypersecreted soluble-Fas (sFas). Secondly, mutation of Fas gene was revealed in rare cases. One of the mutation was 20 bp insertion in the death domain and was deduced to result in the truncated Fas which has no signaling function. Thirdly, aberrant transcripts of caspass-8 were found in all of the ATL cells. In the transcripts 136 bps of the partial intron sequence were inserted, probably producing the truncated form without enzymatically active site. Fourthly, among anti-apoptotic proteins such as FAP-1, FLIP, and survivin, only survivin was up-regulated and suggested to be involved with malignant behavior of the tumor. Finally, about 10% of ATL cases rarely expressed mFas, but sFas, suggesting the advantages for cell survival.
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