Milner A E, Grand R J, Waters C M, Gregory C D
Department of Immunology, University of Birmingham Medical School, UK.
Oncogene. 1993 Dec;8(12):3385-91.
Chromosomal translocation and subsequent de-regulation of the c-myc proto-oncogene are considered to be critical events in the multi-stage evolution of Burkitt lymphoma (BL). It is widely accepted that Myc protein functions as a competence factor for proliferation. However, recent studies indicate that it can also act in some cell types as a regulator of apoptosis. BL cell populations display a high frequency of apoptosis in vivo, a property which is also readily demonstrable in vitro in group I BL cell lines. Such lines are known to retain the cell surface marker characteristics of the parental tumour cells and, in the case of Epstein-Barr virus-positive tumours, their restricted viral protein expression. We have shown previously that apoptosis in a group I BL cell line is inhibited by interferon (IFN)-alpha. Here we show that IFN-alpha-mediated suppression of apoptosis in group I BL cells corresponds temporally with inhibition of Myc protein levels. Furthermore, inhibition of Myc expression following treatment with c-myc anti-sense oligonucleotides markedly enhanced survival of group I BL cells. These results indicate that, whilst c-myc may facilitate cycling of tumour cells in which it is de-regulated, it also stimulates their apoptosis.
染色体易位以及随后c-myc原癌基因的失调被认为是伯基特淋巴瘤（BL）多阶段演变中的关键事件。人们普遍认为Myc蛋白作为增殖的一种感受态因子发挥作用。然而，最近的研究表明，在某些细胞类型中它也可作为凋亡调节因子起作用。BL细胞群体在体内显示出高频率的凋亡，这一特性在I组BL细胞系的体外实验中也很容易得到证实。已知这些细胞系保留了亲代肿瘤细胞的细胞表面标志物特征，并且对于爱泼斯坦-巴尔病毒阳性肿瘤而言，还保留了其有限的病毒蛋白表达。我们之前已经表明，I组BL细胞系中的凋亡受到α干扰素（IFN）的抑制。在此我们表明，IFN-α介导的I组BL细胞凋亡抑制在时间上与Myc蛋白水平的抑制相对应。此外，用c-myc反义寡核苷酸处理后对Myc表达的抑制显著提高了I组BL细胞的存活率。这些结果表明，虽然c-myc可能促进其失调的肿瘤细胞的循环，但它也会刺激这些细胞的凋亡。
