Fas Expression in Tumors

Since it is usually ubiquitous in a variety of hematopoietic and nonhematopoi-etic cells, initial studies of mFas mainly focused on the relationship between the downregulation of mFas and disruption of Fas-mediated apoptosis by which tumor cells may escape elimination. Indeed, some reports support such ideas (L5). However, it was been found that quantitative downregulation of mFas is not always positively associated with tumorigenic properties. Therefore, to understand these issues as they relate to Fas, we consider below the two subjects of quantitatively abnormal regulation of Fas isoforms and qualitative changes due to somatic Fas mutations. 

Both mFas and sFas Are Aberrantly Expressed on ATL Cells 

On the other hand, about 10% of ATL patients have no detectable mFas on the cell surface but have a high sFas level in their sera, with no significant correlation between the mFas and sFas levels. These upregulated sFas properties in ATL consist 

Fas transcripts are known to exist in normal cells in two differently spliced forms—the full-length or alternatively spliced variants encoding iriFas and sFas, respectively. Moreover at least seven variants of alternatively spliced Fas mRNA have been reported in peripheral blood mononuclear cells (PBMC) harvested from normal volunteers. Notably, these variants, encoding mainly sFas, are expressed 

as with many biologically important membrane molecules, the expression of the soluble isoform is also tightly regulated at the level of mRNA transcripts. Consequently, either overproduction or imbalance in density of Fas isoforms is likely to play an important role in the control of Fas-mediated apoptosis in vivo. 

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