Vaux D L, Cory S, Adams J M
Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Australia.
Nature. 1988 Sep 29;335(6189):440-2. doi: 10.1038/335440a0.
A common feature of follicular lymphoma, the most prevalent haematological malignancy in humans, is a chromosome translocation (t(14;18] that has coupled the immunoglobulin heavy chain locus to a chromosome 18 gene denoted bcl-2. By analogy with the translocated c-myc oncogene in other B-lymphoid tumours bcl-2 is a candidate oncogene, but no biological effects of bcl-2 have yet been reported. To test whether bcl-2 influences the growth of haematopoietic cells, either alone or together with a deregulated c-myc gene, we have introduced a human bcl-2 complementary DNA using a retroviral vector into bone marrow cells from either normal or E mu-myc transgenic mice, in which B-lineage cells constitutively express the c-myc gene. Bcl-2 cooperated with c-myc to promote proliferation of B-cell precursors, some of which became tumorigenic. To determine how bcl-2 expression impinges on growth factor requirements, the gene was introduced into a lymphoid and a myeloid cell line that require interleukin 3 (IL-3). In the absence of IL-3, bcl-2 promoted the survival of the infected cells but they persisted in a G0 state, rather than proliferating. These results argue that bcl-2 provided a distinct survival signal to the cell and may contribute to neoplasia by allowing a clone to persist until other oncogenes, such as c-myc, become activated.
滤泡性淋巴瘤是人类最常见的血液系统恶性肿瘤，其一个常见特征是染色体易位（t(14;18)），该易位将免疫球蛋白重链基因座与18号染色体上一个名为bcl-2的基因连接在一起。与其他B淋巴细胞肿瘤中易位的c-myc癌基因类似，bcl-2是一个候选癌基因，但尚未有关于bcl-2生物学效应的报道。为了检测bcl-2是否单独或与失调的c-myc基因共同影响造血细胞的生长，我们使用逆转录病毒载体将人bcl-2互补DNA导入正常或Eμ-myc转基因小鼠的骨髓细胞中，在Eμ-myc转基因小鼠中，B系细胞组成性表达c-myc基因。bcl-2与c-myc协同促进B细胞前体的增殖，其中一些前体变成了致瘤性的。为了确定bcl-2表达如何影响对生长因子的需求，将该基因导入需要白细胞介素3（IL-3）的一个淋巴细胞系和一个髓细胞系中。在没有IL-3的情况下，bcl-2促进了被感染细胞的存活，但它们停留在G0状态，而不是增殖。这些结果表明，bcl-2为细胞提供了一个独特的存活信号，并且可能通过允许一个克隆持续存在直到其他癌基因（如c-myc）被激活而促进肿瘤形成。
