Overexpression of the human BCL-2 gene product results in growth enhancement of Epstein-Barr virus-immortalized B cells.
Overexpression of the human BCL-2 gene product results in growth enhancement of Epstein-Barr virus-immortalized B cells.
复制标题
人类 BCL-2 基因产物的过度表达导致 Epstein-Barr 病毒永生化 B 细胞的生长增强。
DOI：
--
复制
发表时间：
1989
影响因子：
11.1
通讯作者：
Y. Tsujimoto
中科院分区：
文献类型：
--
作者：
Y. Tsujimoto
人BCL-2基因产物的生物活性在用由猿猴病毒40启动子和增强子驱动的BCL-2序列转染的EB病毒（EBV）感染的人淋巴母细胞样B细胞系中进行分析。BCL-2蛋白的过量产生赋予EBV感染的B细胞选择性生长优势，如与低血清培养基中的对照转染子相比以及在有限稀释接种后对EBV感染的B细胞的选择性生长优势，但不使细胞在无胸腺裸鼠中致瘤。在用BCL-2基因转染的细胞中也观察到这种生长增强，BCL-2基因自身的启动子与免疫球蛋白重链基因增强子并列，这代表了在滤泡性淋巴瘤中观察到的BCL-2基因的易位形式，具有t（14;18）易位。过量产生BCL-2蛋白的EBV感染的B细胞的生长优势既不是由于生长因子产生的增加，也不是由于BCL-2转染子对白细胞介素1或6的敏感性的增加，尽管已知这两种淋巴因子刺激EBV感染的B细胞系的增殖。EB病毒感染的B细胞通过过度产生BCL-2蛋白而获得的生长优势表明BCL-2基因产物直接参与滤泡性淋巴瘤的发病机制。
The biological activity of the human BCL-2 gene product was analyzed in an Epstein-Barr virus (EBV)-infected human lymphoblastoid B-cell line transfected with BCL-2 sequences driven by the simian virus 40 promoter and enhancer. Overproduction of the BCL-2 protein conferred a selective growth advantage to the EBV-infected B cells as selective growth advantage to the EBV-infected B cells as compared with control transfectants in low-serum medium and also after seeding at limiting dilution but did not render the cells tumorigenic in athymic nude mice. This growth enhancement was also seen in cells transfected with the BCL-2 gene with its own promoter juxtaposed to the immunoglobulin heavy chain gene enhancer, which represents the translocated form of the BCL-2 gene observed in follicular lymphomas with the t(14;18) translocation. The growth advantage of EBV-infected B cells overproducing the BCL-2 protein is neither due to the enhanced growth factor production nor due to an enhanced sensitivity of the BCL-2 transfectants to interleukins 1 or 6, although both lymphokines are known to stimulate proliferation of EBV-infected B-cell lines. The growth advantage of EBV-infected B cells by overproduction of the BCL-2 protein suggests the direct involvement of the BCL-2 gene product in the pathogenesis of follicular lymphoma.