The Cell-Cycle Control of Astrocytes and Astrocytomas

星形胶质细胞和星形细胞瘤的细胞周期控制

基本信息

  • 批准号:
    6540521
  • 负责人:
  • 金额:
    $ 21.76万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-07-15 至 2005-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This year, and in every year in the foreseeable future, 17,000 Americans will develop primary brain cancers. Of these, the most common tumor is astrocytoma. Of the 8,000 people to be diagnosed with astrocytoma, all will eventually die of their disease. The vulnerability of the astrocyte to transformation lies in its ability to re-enter the cell-cycle at any point in the life-time of an organism. In spite of the ability to proliferate, astrocytes are kept mostly quiescent, except in response to disease or trauma, where there is a concomitant neuronal loss. A number of years ago, we and others demonstrated that astrocyte proliferative control is effected by contact with neuronal membranes, although the precise molecular mechanism by which neurons exert this control has remained elusive. My laboratory has recently identified a receptor on the surface of the astrocyte, CD8 1, which is absolutely required for neuron-induced astrocyte cell-cycle arrest (see Preliminary Data, and appended manuscript for details). In this application, we propose a series of biochemical, molecular and cell biological experiments aimed at the identification and characterization of neuronal CD8 1 binding proteins. In addition, we will begin to query the astrocytic signaling mechanism following neuronal binding. Our findings for the requirement for astrocyte expressed CD8 1 for neuron-induced growth control takes on added significance, based on our observation that all of the astrocytoma cell lines we have examined to date have absolutely down regulated CD8 1 protein and message. To determine if CD8 1 expression can rescue the ability of these cells to respond to neuron-induced by cell-cycle arrest, we have expressed a CD8 1 -GFP fusion construct in the astrocytoma cell lines. The transfectants will be assayed for in vitro neuronal responsiveness, and in vivo tumor progression and metastasis in nude mice. In parallel with these experiments, we will continue a series of affinity chromatographic purification of neuronal membrane proteins that are active inhibitors of astrocyte proliferation. While we hope and anticipate that our two lines of inquiry on neuronal mediators of astrocyte growth control will converge, it is quite possible that we will identify separate, redundant mechanisms that are involved in maintaining CNS numerical homeostasis.
描述(由申请人提供):今年,在每一年

项目成果

期刊论文数量(0)
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DAVID E WEINSTEIN其他文献

DAVID E WEINSTEIN的其他文献

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{{ truncateString('DAVID E WEINSTEIN', 18)}}的其他基金

Optimization of GMAK to treat glioblastoma multiforme
GMAK 治疗多形性胶质母细胞瘤的优化
  • 批准号:
    7107363
  • 财政年份:
    2006
  • 资助金额:
    $ 21.76万
  • 项目类别:
Characterization of the role of hepcidin in the anemia of chronic disease.
铁调素在慢性病贫血中作用的表征。
  • 批准号:
    6975166
  • 财政年份:
    2004
  • 资助金额:
    $ 21.76万
  • 项目类别:
Clinical Evaluation of Portable Lactate Meter in Type Glycogen Storage Disease
便携式乳酸计在型糖原贮积病中的临床评价
  • 批准号:
    6975186
  • 财政年份:
    2004
  • 资助金额:
    $ 21.76万
  • 项目类别:
Assessment of abnormal glycogen synthesis as a cause of ketotic hypoglycemia
糖原合成异常作为酮症低血糖原因的评估
  • 批准号:
    6975121
  • 财政年份:
    2004
  • 资助金额:
    $ 21.76万
  • 项目类别:
Correlation of Markers of Metabolic Control with Complications in GSD.
代谢控制标志物与 GSD 并发症的相关性。
  • 批准号:
    6975165
  • 财政年份:
    2004
  • 资助金额:
    $ 21.76万
  • 项目类别:
Characterization of anemia of chronic disease in type l
l型慢性病贫血的特征
  • 批准号:
    6975167
  • 财政年份:
    2004
  • 资助金额:
    $ 21.76万
  • 项目类别:
Refinement of GM1416-a Drug to Treat Neurodegeneration
治疗神经退行性疾病药物 GM1416 的精制
  • 批准号:
    6590954
  • 财政年份:
    2003
  • 资助金额:
    $ 21.76万
  • 项目类别:
The Cell-Cycle Control of Astrocytes and Astrocytomas
星形胶质细胞和星形细胞瘤的细胞周期控制
  • 批准号:
    6665187
  • 财政年份:
    2001
  • 资助金额:
    $ 21.76万
  • 项目类别:
The Cell-Cycle Control of Astrocytes and Astrocytomas
星形胶质细胞和星形细胞瘤的细胞周期控制
  • 批准号:
    6762366
  • 财政年份:
    2001
  • 资助金额:
    $ 21.76万
  • 项目类别:
The Cell-Cycle Control of Astrocytes and Astrocytomas
星形胶质细胞和星形细胞瘤的细胞周期控制
  • 批准号:
    6369209
  • 财政年份:
    2001
  • 资助金额:
    $ 21.76万
  • 项目类别:

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