Sugahara K, Yamada Y, Hiragata Y, Matsuo Y, Tsuruda K, Tomonaga M, Maeda T, Atogami S, Tsukasaki K, Kamihira S
Department of Laboratory Medicine, Nagasaki University School of Medicine, Nagasaki City, Japan.
Int J Cancer. 1997 Jul 3;72(1):128-32. doi: 10.1002/(sici)1097-0215(19970703)72:1<128::aid-ijc18>3.0.co;2-f.
Fas, also designated as Apo-1 and CD95, is a cell membrane receptor (mFas) involved in apoptotic cell death. A soluble form (sFas) lacking the transmembrane domain due to alternative splicing has been isolated. Abnormal expression of sFas and mFas is likely to be involved in lymphoproliferative disorders and auto-immune diseases. Adult T-cell leukemia (ATL) caused by human T-cell-leukemia virus type-1 (HTLV-1) is well known to be a T-cell neoplasm with strong mFas expression, suggesting a role of Fas in the pathology of the disease. We examined protein and 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 in malignant ATL. However, expression of the isoforms in some cases of ATL varied; there was no mFas expression on the cell surface and sFas levels were high in serum. In contrast, all ATL cell lines examined showed strong mFas expression and scarce production of sFas in the supernatant, corresponding to strong expression of full-length Fas mRNA and weak to negative expression of alternatively spliced mRNA lacking the transmembrane domain. Our findings indicate that the mode of expression of Fas isoforms in ATL cells is not always homogenous and that Fas may play a role in the malignant behavior and oncogenesis of ATL.
Fas，也被称为Apo-1和CD95，是一种参与细胞凋亡性死亡的细胞膜受体（mFas）。已分离出一种由于可变剪接而缺乏跨膜结构域的可溶性形式（sFas）。sFas和mFas的异常表达可能与淋巴增生性疾病和自身免疫性疾病有关。由1型人类T细胞白血病病毒（HTLV-1）引起的成人T细胞白血病（ATL）是一种众所周知的具有强mFas表达的T细胞肿瘤，提示Fas在该疾病的病理过程中发挥作用。我们检测了新鲜ATL细胞和ATL细胞系中Fas两种异构体的蛋白质和mRNA表达。一般来说，mFas在ATL细胞中强烈表达，血清中的sFas水平较高，尤其是在恶性ATL中。然而，在某些ATL病例中，异构体的表达有所不同；细胞表面没有mFas表达，血清中sFas水平较高。相反，所有检测的ATL细胞系均显示出强mFas表达，而上清液中sFas产生较少，这与全长Fas mRNA的强表达以及缺乏跨膜结构域的可变剪接mRNA的弱至阴性表达相对应。我们的研究结果表明，ATL细胞中Fas异构体的表达模式并不总是一致的，并且Fas可能在ATL的恶性行为和肿瘤发生中发挥作用。
