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

为了评估通过v-转化的靶细胞范围， 以及确定V-raf是否能够诱导 或需要与第二个 癌基因myc，构建了一系列重组病毒 在3611-鼠肉瘤上具有病毒癌基因之一或两者 病毒（MSV）背景。 两种癌基因的组合， 感染性小鼠逆转录病毒（J-2）诱导造血干细胞 肿瘤，除了不太突出的纤维肉瘤和 胰腺腺癌接种后1至3周。 的 血液肿瘤包括T-淋巴细胞免疫母细胞淋巴瘤， B细胞谱系和成红细胞增多症。 平行于 两种癌基因对造血细胞协同作用 在体内，我们发现raf癌基因诱导的骨转化 培养物中的骨髓细胞通过加入myc而增强， 当这些细胞在标准培养基中生长时 媒体 我们的结论是raf和myc的共同表达 造血细胞中的癌基因改变了它们各自的 转化活动。 myc对此的贡献 通过使用一系列重组鼠 能够表达禽类V-myc或小鼠C-myc的逆转录病毒， 研究myc表达改变对 造血/淋巴细胞。 携带v-myc的病毒J-3， 显示出与矿物油，降植烷，在诱导 在浆细胞瘤中，它在功能上取代了c- myc通过染色体易位。 白细胞介素-3（IL-3） 3)-或IL-2依赖性细胞系，引入重组 病毒消除了生长对IL-3或IL-2的需要， 与此相关的是c-myc表达的抑制。 的 结果表明myc是信号中的一个成分， IL-3和IL-2的转导途径，并支持 c-myc表达的自动调节机制。 相对于V- 原代淋巴/造血细胞中v-raf的表达 具有不朽的功能，但不废除要求 IL-3促进生长

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.