SOLUBLE AND MEMBRANE ISOFORMS OF FAS CD95 IN FRESH ADULT T-CELL LEUKEMIA (ATL) CELLS AND ATL-CELL LINES/

Fas, also designated as Apo-1 and CD95, is a cell membrane receptor (m Fas) involved in apoptotic cell death, A soluble form (sFas) lacking t he transmembrane domain due to alternative splicing has been isolated, Abnormal expression of sFas and mFas is likely to be involved in lymp hoproliferative disorders and auto-immune diseases, Adult T-cell leuke mia (ATL) caused by human T-cell-leukemia virus type-I (HTLV-1) Is wel l known to be a T-cell neoplasm with strong mFas expression, suggestin g a role of pas in the pathology of the disease, We examined protein a nd mRNA expression of the 2 isoforms of Fas in fresh ATL cells and ATL cell lines, In general, mFas was strongly expressed in ATL cells, and sFas levels in sera were high, especially Tn malignant ATL, However, expression of the isoforms in some cases of ATL varied; there was no m Fas expression on the cell surface and sFas levels were high in serum. In contrast, all ATL cell lines examined showed strong mFas expressio n and scarce production of sFas in the supernatant, corresponding to s trong expression of full-length Fas mRNA acid weak to negative express ion of alternatively spliced mRNA lacking the transmembrane domain, Ou r findings indicate that the mode of expression of Fas isoforms in ATL . tells is not always homogenous and that Fas may play a Pole in the m alignant behavior and oncogenesis of ATL. (C) 1997 Wiley-Liss, Inc.