RNA-TUMOR VIRUS--HEMATOPOIETIC CELL INTERACTION

许多逆转录病毒在注射到适当的宿主中时诱发肿瘤， 因此是研究控制致癌事件的有用工具 过程 快速转化的病毒特别适合于这种情况。 因为它们似乎是通过直接干扰 正常的生长和分化。 一般来说，这些病毒已经失去了大部分 或复制型逆转录病毒的所有基因， 与正常细胞DNA密切相关的序列，称为共序列或 onc基因。 虽然在许多情况下缺乏正式的证明， 这些病毒的onc基因似乎负责病毒的能力， 来诱发肿瘤和转化细胞。 尽管onc基因的产物 最初是通过它们诱导肿瘤和转化的能力来确定的 细胞，最近的证据表明，表达相同的“转化”， 蛋白质在不同的细胞类型可以有不同的效果。 比如说， 尽管Abelson病毒感染某些造血细胞诱导 淋巴样细胞的转化，造血细胞衍生的感染 从早期胚胎组织诱导生长和分化， 红系细胞 此外，尽管A-MuLV将一些 成纤维细胞样细胞系，该病毒对其他细胞是致命的。 模式 病毒onc基因的作用和正常序列的作用， 可能在生长和分化中起作用，目前尚不清楚。 对这个问题的研究是实现 通过快速转化了解肿瘤发生的机制 逆转录病毒 此外，还需要了解 正常的细胞信息被破坏，导致 恶性肿瘤，具有超越逆转录病毒-细胞相互作用的含义。 解决 针对这一问题，我们选择了造血细胞模型系统进行研究 并检查两种不相关的ONC蛋白表达的结果， P160 v-ab 1，由Abelson鼠白血病病毒编码，P21 v-ras，由Abelson鼠白血病病毒编码， 哈维鼠肉瘤病毒

Many retroviruses induce tumors when injected into appropriate hosts and thus are useful tools to study the events controlling the oncogenic process. Rapidly transforming viruses are particularly well suited to such studies because they seem to cause tumors by directly interfering with normal growth and differentiation. Generally, these viruses have lost most or all of the genes of replication competent retroviruses and acquired sequences closely related to normal cellular DNA called on cosequences or onc genes. Although formal proof is lacking in many cases, the expression of these viral onc genes appears to be responsible for the virus' ability to induce tumors and transform cells. Although the products of onc genes were originally identified by their ability to induce tumors and transform cells, recent evidence indicates that expression of the same "transforming" protein in different cell types can have different effects. For example, although Abelson virus infection of some hematopoietic cells induces transformation of lymphoid cells, infection of hematopoietic cells derived from early embryonic tissues induces growth and differentiation of erythroid cells. In addition, although A-MuLV transforms some fibroblastoid cell lines, the virus is lethal to others. The mode of action of viral onc genes and the role the normal sequences from which they were derived may play in growth and differentiation are presently unclear. Examination of this question is an important step toward achieving an understanding of the mechanism of oncogenesis by rapidly transforming retroviruses. In addition, an understanding of the mechanism(s) by which normal cellular information is subverted, leading to the development of malignancy, has implication beyond retrovirus-cell interaction. To address this question, we have chosen to study a hematopoietic cell model system and examine the consequences of expression of two unrelated onc proteins, P160 v-ab1, encoded by Abelson murine leukemia virus and P21 v-ras, encoded by Harvey murine sarcoma virus.