SUBSTITUTE RAS FOR HERPESVIRUS SAIMIRI STP ONCOGENE IN LYMPHOCYTE TRANSFORMATION

STP-C488（松鼠猴疱疹病毒[HVS] C组毒株488的STP [C488]）是唯一发现与 细胞ras和激活ras信号转导通路 研究ras信号转导在 STP依赖的生长转化，我们构建了重组 其中STP-C488癌基因被替换为 细胞正常ras（c-ras）或病毒致癌ras（v-ras）重组 HVS STP/v-ras永生化原代普通绒猴T淋巴细胞， 白细胞介素-2非依赖性生长与野生型HVS C488一样有效 (wt而重组HVS STP/c-ras则效率较低 而wt HVS永生化的CD 4-CD 8+单阳性T淋巴细胞， HVS STP/c-ras-和HVS STP/v-ras-永生化细胞主要是 CD 4 + CD 8+双阳性T淋巴细胞 STP/v-ras永生化T细胞显示高水平的ras表达 并表现出粘附性巨噬细胞样形态学。 可能是由于AP-1转录因子的剧烈激活引起的。 最后，HVS STP/v-ras和HVS STP/c-ras各自诱导 淋巴瘤的两个常见的绒猴之一，虽然发病是 这些结果表明，ras可以 替代HVS C488的STP癌基因， 初级淋巴细胞的生长和ras的活化形式 比正常细胞形式的ras更有效 出版物Guo，J，威廉姆斯，K，Duboise，SM，亚历山大，L，Veazey，R 和Jung，JU用ras替代松鼠猴疱疹病毒STP 淋巴细胞转化中的癌基因J Virol 1998; 72：3698-3704

STP-C488 (STP of herpesvirus saimiri [HVS] group C strain 488 [C488]) is the only virus-encoded protein found to associate with cellular ras and activate ras signal transduction pathways To investigate an important role for ras signal transduction in STP-dependent growth transformation, we constructed recombinant strains of HVS C488 in which the STP-C488 oncogene was replaced with cellular normal ras (c-ras) or viral oncogenic ras (v-ras) Recombinant HVS STP/v-ras immortalized primary common marmoset T lymphocytes to inter-leukin-2-independent growth as efficiently as wild-type HVS C488 (wt HVS), while recombinant HVS STP/c-ras did so with low efficiency Whereas wt HVS immortalized CD4- CD8+ single-positive T lymphocytes, HVS STP/c-ras- and HVS STP/v-ras-immortalized cells were principally CD4+ CD8+ double-positive T lymphocytes In addition, HVS STP/v-ras-immortalized T cells showed a high level of ras expression and exhibited an adherent macrophage-like morphol ogy These phenotypes were likely caused by the drastic activation of AP-1 transcriptional factor activity Finally, HVS STP/v-ras and HVS STP/c-ras each induced lymphoma in one of two common marmosets, although onset of disease was more rapid with the v-ras virus These results demonstrate that ras can substitute for the STP oncogene of HVS C488 to allow immortalized growth of primary lymphoid cells and that an activated form of ras does so more efficiently than the normal cellular form of ras PUBLICATIONS Guo, J, Williams, K, Duboise, SM, Alexander, L, Veazey, R and Jung, JU Substitution of ras for the herpesvirus saimiri STP oncogene in lymphocyte transformation J Virol 1998; 72:3698-3704