SUBSTITUTE RAS FOR HERPESVIRUS SAIMIRI STP ONCOGENE IN LYMPHOCYTE TRANSFORMATION

在淋巴细胞转化中用 RAS 替代疱疹病毒 SAIMIRI STP 癌基因

• 批准号: 6591297
• 负责人: JIE GUO
• 金额: $ 11.11万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6591297
• 关键词: Mammalia; animal tissue; communicable diseases; virus

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

STP-C488（疱疹病毒 saimiri [HVS] C 组毒株 488 的 STP [C488]）是唯一被发现与 细胞ras并激活ras信号转导通路 研究ras信号转导的重要作用 STP依赖的生长转化，我们构建了重组 HVS C488 菌株，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 永生化原代普通狨猴 T 淋巴细胞 不依赖白介素 2 的生长与野生型 HVS C488 一样有效 (wt HVS)，而重组 HVS STP/c-ras 效率较低 而wt HVS永生化CD4-CD8+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 CD4+ CD8+ 双阳性 T 淋巴细胞 此外，HVS STP/v-ras-永生化T细胞显示出高水平的ras表达 并表现出粘附性巨噬细胞样形态 这些表型 可能是由 AP-1 转录的剧烈激活引起的 最后，HVS STP/v-ras 和 HVS STP/c-ras 各自诱导 两种常见狨猴之一的淋巴瘤，尽管疾病的发作是 v-ras 病毒的速度更快 这些结果表明 ras 可以 替代 HVS C488 的 STP 癌基因，实现永生化 原代淋巴细胞的生长和 ras 的激活形式 比正常细胞形式的 ras 更有效 出版物Guo, J、Williams, K、Duboise, SM、Alexander, L、Veazey, R 和 Jung, JU 用 ras 替换疱疹病毒 saimiri STP 淋巴细胞转化中的癌基因 J Virol 1998； 72:3698-3704