ROLE OF RAF AND MYC ONCOGENES IN TRANSFORMATION IN VIVO AND IN VITRO

为了评估目标单元格范围以通过v- 以及确定v-RAF是否能够诱导 转换本身或需要与第二个 癌基因myc，构建了一系列重组病毒。 一种或两种病毒癌基因对3611-小鼠肉瘤的作用 病毒(MSV)背景。两种癌基因在一种 感染性小鼠反转录病毒(J-2)诱导造血 肿瘤，除了不太突出的纤维肉瘤和 胰腺癌接种后1~3周。这个 血液肿瘤由T-免疫母细胞性淋巴瘤组成。 B细胞血统和红细胞增多症。在与 两种癌基因对小鼠骨髓造血细胞的协同作用 体内，我们发现RAF癌基因诱导的骨转化 培养中的骨髓细胞通过添加myc而得到增强，myc 当这些细胞在标准条件下培养时，其本身并不能转化这些细胞 媒体。我们得出结论：RAF和myc的同时表达 造血细胞中的癌基因改变了它们各自的 转型活动。MYC对此的贡献 通过使用一系列重组小鼠来检验协同作用 能表达禽v-myc或鼠c-myc的逆转录病毒 研究myc基因表达改变对血管内皮细胞生长的影响 造血细胞/淋巴样细胞。携带v-myc的病毒J-3是 显示出在诱导过程中与矿物油、普里斯坦有协同作用 在浆细胞瘤中，它在功能上取代c- MYC由染色体易位引起。与白介素3(IL-3) 3)-或IL-2依赖的细胞系，引入重组 病毒消除了生长所需的IL-3或IL-2， 与此相关的是c-myc表达的抑制。这个 研究结果表明，myc是信号中的一个组成部分。 IL-3、IL-2的信号转导途径与支持血管生成 C-myc基因表达的自我调节机制。与v-对比- MYC，v-RAF在原始淋巴/造血细胞的表达 在不取消要求的情况下具有不朽的功能 为了IL-3的生长。

In order to evaluate the target cell range for transformation by v- raf, as well as to determine whether v-raf is capable of inducing transformation by itself or requires interaction with a second oncogene, myc, a series of recombinant viruses was constructed with either or both viral oncogenes on the 3611-murine sarcoma virus (MSV) background. A combination of both oncogenes in an infectious murine retrovirus (J-2) induces hematopoietic neoplasms, in addition to less prominent fibrosarcomas and pancreatic adenocarcinomas 1 to 3 weeks after inoculation. The hematologic neoplasms consist of immunoblastic lymphomas of T- and B-cell lineage, and erythroblastosis. In parallel to the synergistic action of both oncogenes on hematopoietic cells in vivo, we find that raf oncogene-induced transformation of bone marrow cells in culture is enhanced by the addition of myc, which by itself does not transform these cells when grown in standard media. We conclude that concomitant expression of raf and myc oncogenes in hematopoietic cells alters their respective transforming activities. The contribution of myc to this synergism was examined by using a series of recombinant murine retroviruses capable of expressing avian v-myc or mouse c-myc to study the effect of altered myc expression on hematopoietic/lymphoid cells. The v-myc-carrying virus, J-3, was shown to synergize with the mineral oil, pristane, in the induction of plasmacytomas, where it functionally replaces activation of c- myc by chromosomal translocation. With either interleukin-3 (IL- 3)- or IL-2-dependent cell lines, introduction of the recombinant viruses abrogated the requirement for IL-3 or Il-2 for growth, and associated with this was the suppression of c-myc expression. The findings suggest that myc is a component in the signal transduction pathway for IL-3 and IL-2 and support an autoregulatory mechanism of c-myc expression. In contrast to v- myc, expression of v-raf in primary lymphoid/hematopoietic cells has an immortalizing function without abrogating the requirement for IL-3 for growth.