Gazitt Y, Hu W X
Department of Medicine, Division of Hematology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284, USA.
Int J Oncol. 1998 Jan;12(1):211-20.
Eight myeloma cell lines with variable expression of bcl-2 were screened for the expression of the FAS antigen and for sensitivity to anti-FAS-induced apoptosis. Anti-FAS-induced apoptosis correlated positively (R = 0.89) with the level of expression of the FAS antigen, and was independent of the expression of bcl-2. Forced expression of bcl-2 in 8226 and ARP-1 multiple myeloma (MM) cell lines expressing relatively low levels of bcl-2, resulted in 1-2 log increase in resistance to dexamethasone (DEX)-induced apoptosis. However, sensitivity to anti-FAS-induced apoptosis was unchanged in ARP-1 cells or was increased in 8226 cells, compared to the parental cell lines. The increased sensitivity to anti-FAS-induced apoptosis in 8226 cells was due to the increase in FAS expression in the bcl-2 transfected cells and was proportionate to the increase in FAS expression. Furthermore, we observed manyfold increase in the expression of Fas, CD40, CD45 and CD19 antigens, in 8226 cells, concomitant with a significant decrease in the expression of CD38 antigen. Thus, 8226 cells overexpressing bcl-2 appear to have an immature myeloma cell phenotype, have higher growth-rate and increased sensitivity to anti-FAS-induced apoptosis.
对8种bcl-2表达各异的骨髓瘤细胞系进行FAS抗原表达及抗FAS诱导凋亡敏感性的筛选。抗FAS诱导的凋亡与FAS抗原表达水平呈正相关（R = 0.89），且与bcl-2的表达无关。在bcl-2表达相对较低的8226和ARP-1多发性骨髓瘤（MM）细胞系中强制表达bcl-2，导致对地塞米松（DEX）诱导凋亡的抗性增加1 - 2个对数。然而，与亲代细胞系相比，ARP-1细胞对抗FAS诱导凋亡的敏感性未变，而8226细胞的敏感性增加。8226细胞对抗FAS诱导凋亡敏感性的增加是由于bcl-2转染细胞中FAS表达增加，且与FAS表达的增加成比例。此外，我们观察到8226细胞中Fas、CD40、CD45和CD19抗原的表达增加了许多倍，同时CD38抗原的表达显著降低。因此，过表达bcl-2的8226细胞似乎具有未成熟骨髓瘤细胞表型，生长速率更高，对抗FAS诱导凋亡的敏感性增加。
