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C-MYC EXPRESSION AND APOPTOSIS IN A B CELL LINE

C-MYC EXPRESSION AND APOPTOSIS IN A B CELL LINE
B 细胞系中的 C-MYC 表达和凋亡
批准号:
2089091
负责人:
GAIL E. SONENSHEIN
金额:
$18.71万
依托单位国家:
美国
项目类别:
财政年份:
1984
资助国家:
美国
项目状态:
已结题
起止时间:
1984-01-01 至 1997-01-31

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中文摘要
翻译
细胞凋亡或程序性细胞死亡(PCD)是细胞的一种普遍机制 与B淋巴细胞耐受性有关的自杀。为 例如,治疗小鼠早期B淋巴瘤WEHI 231株,一个模型 为研究B细胞的耐受性,用其表达的抗血清 表面IgM,如山羊抗鼠Ig(GaMIg)或抗MU抗血清, 通过细胞凋亡抑制其增殖。DNA的寡体降解 在治疗后12小时内可被检测到。最近的证据表明 证明了原癌基因c-myc的表达是 对PCD是必需的,以剂量依赖的方式促进细胞凋亡。这里 利用WEHI231细胞系研究c-myc在细胞凋亡中的作用 作为模范系统。C-myc在WEHI 231细胞中的表达及意义 细胞凋亡的影响已经被广泛地描述为正在进行的工作 私家侦探和其他实验室的。人参皂苷对WEHI231细胞的作用 GaMIg导致c-myc RNA表达最初增加5-to 10倍的1-2小时,然后是4-6小时的戏剧性下降 治疗后数小时。C-myc蛋白的合成与早期相似 RNA水平的变化;此外,蛋白质是瞬时的 在1小时内过度磷酸化。到24小时,信使核糖核酸和蛋白质水平 远低于在对照细胞中观察到的结果。一个主要的控制地点 C-myc rna表达的这些变化是在转录过程中介导的。 水平。C-myc表达的增加似乎对 细胞凋亡。例如,私家侦探的实验室最近显示 WEHI231株抗Delta抗血清稳定治疗的研究 转染有Delta重链(WEHI 231-Delta),不能 诱导细胞凋亡,未能诱导c-myc蛋白水平,相比之下 用抗MU血清治疗。因此,这项建议的目标是1) 检测抗Ig治疗对c-myc蛋白表达的影响 2)鉴定介导c-myc变化的转录因子 核糖核酸水平;将特别强调核因素 核因子-KB,PI的实验室已经证明在其中发挥重要作用 C-myc转录调控。具体来说,翻译后 C-myc的修饰及其与其他细胞蛋白的结合将 接受检查。细胞因子变化的生化性质和功能效应 将检测在细胞凋亡过程中注意到的核因子-kB的表达。结果 将通过使用WEHI231-delta线与细胞凋亡相关。 这些研究应该为控制艾滋病提供重要的见解。 淋巴细胞的凋亡、B细胞耐受的形成和 C-myc癌基因在这些过程中的作用。
英文摘要
Apoptosis or programmed cell death (PCD) is a general mechanism of cell suicide that has been implicated in tolerization of B lymphocytes. For example, treatment of the murine early B lymphoma WEHI 231 line, a model for study of B cell tolerance, with an antiserum against its expressed surface IgM, such as goat anti-mouse Ig (GaMIg) or anti-mu antisera, inhibits its proliferation via apoptosis. Oligosomal degradation of DNA is detectable by 12 hours post-GaMIg treatment. Recent evidence has demonstrated that the expression of the nuclear proto-oncogene c-myc is necessary for PCD, promoting apoptosis in a dose-dependent fashion. Here the role of c-myc in apoptosis will be explored using the WEHI 231 line as model system. The expression of c-myc in WEHI 231 cells and the effects of apoptosis have been extensively characterized by ongoing work from the PI's and other laboratories. Treatment of WEHI 231 cells with GaMIg results in an initial increase in expression of c-myc RNA of 5- to 10-fold by 1-2 hours, which is followed by a dramatic decline by 4-6 hours post-treatment. The synthesis of c-myc protein parallels the early changes in RNA levels; furthermore, the protein is transiently hyperphosphorylated at 1 hour. By 24 hours, mRNA and protein levels are well below those observed in control cells. A major site of control of these changes in c-myc RNA expression is mediated at the transcription level. The increase in c-myc expression appears to be critical for apoptosis. For example, the PI's laboratory has recently shown that treatment with an anti-delta antiserum of a WEHI 231 line stably transfected with a delta heavy chain (WEHI 231-delta), which fails to induce apoptosis, failed to induce c-myc protein levels, in contrast to treatment with anti-mu serum. Thus the aims of this proposal are to 1) measure the effects of anti-Ig treatment on c-myc protein expression, and 2) characterize the transcription factors mediating the changes in c-myc RNA levels; particular emphasis, will be placed on the nuclear factor NF-KB, which the PI's laboratory has demonstrated plays a major role in regulation of c-myc transcription. Specifically, post-translational modifications and association of c-myc with other cellular proteins will be examined. The biochemical nature and functional effects of changes in expression of NF-KB, noted during apoptosis, will be measured. Results will be correlated with apoptosis through use of the WEHI 231-delta line. These studies should provide important insights into the control of apoptosis in lymphocytes, the development of B cell tolerance and the role of the c-myc oncogene in these processes.
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Development of a Companion Diagnostic Assay for Detection of ADAM8-Positive Cancers
  • 批准号:
    10685491
  • 项目类别:
  • 资助金额:
    $100.0万
  • 财政年份:
    2022
  • 负责人:
    GAIL E. SONENSHEIN
  • 依托单位:
Development of a Companion Diagnostic Assay for Detection of ADAM8-Positive Cancers
  • 批准号:
    10545124
  • 项目类别:
  • 资助金额:
    $100.0万
  • 财政年份:
    2022
  • 负责人:
    GAIL E. SONENSHEIN
  • 依托单位:
Antibody targeting of ADAM8 for treatment of triple-negative breast cancer
  • 批准号:
    9984632
  • 项目类别:
  • 资助金额:
    $0.21万
  • 财政年份:
    2016
  • 负责人:
    GAIL E. SONENSHEIN
  • 依托单位:
Antibody targeting of ADAM8 for treatment of triple-negative breast cancer
  • 批准号:
    9047902
  • 项目类别:
  • 资助金额:
    $30.0万
  • 财政年份:
    2016
  • 负责人:
    GAIL E. SONENSHEIN
  • 依托单位:
海外基金