SIGNAL TRANSDUCTION EVENTS AND HE REGULATION OF CELL GROWTH
信号转导事件和细胞生长的调节
基本信息
- 批准号:3874460
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Prostate cancer is the second most common cause of cancer death in men in
the United States. The only treatment for advanced disease is hormonal
therapy, which is not curative. Hormonal therapy is severely limited
because androgen-dependent tumor typically becomes androgen independent
Although there has been a considerable amount of work on the regulation of
prostatic cell growth by androgen and the molecular events following
androgen withdrawal, relatively little is known about the receptors
expressed by androgen-independent prostate carcinoma cells. We have been
working on new approaches to the treatment of this neoplasm through
identification of novel cell surface receptors that transmit a growth
inhibitory signal through activation of the phosphatidyhnositol signal
through activation of the phosphatidylinositol signal transduction pathway
and mobilization of intracellular Ca(2+). Twelve hormones and
neurotransmitters stimulated an increase in cytoplasmic free Ca(2+) in
human androgren-independent prostate carcinoma cell lines. Stimulation of
the plasma membrane receptor for adenine nucleotides, the P2 purinergic
receptor, consistently caused a massive increase in Ca(2+) release, close
to the total intracellular releasable Ca(2+). Studies with Ca(2+) channel
blockers and EGTA demonstrated that this response derived approximately 50%
from release from internal stores and 50% from the opening of
dihydropyridine-sensitive plasma membrane Ca(2+) channels. High pressure
liquid chromatographic analysis of inositol phosphate isomers showed a
purinoceptor-linked increase in phosphatidylinositol turnover. Treatment
with ATP or the non-hydrolyzable analog adenyhmidodiphosphate induced a
marked change in cell morphology, including chromatin condensation and
nucleolar degeneration, and significantly inhibited cell growth in vitro.
Normal prostatic cells are triggered to undergo programmed cell death in
response to androgen withdrawal. This response can be inhibited by Ca(2+)
channel blockers. Our data suggest that it may be possible to circumvent
the absence of androgen receptors in androgen-independent prostate
carcinoma cells, and trigger a cytotoxic response through activation of a
Ca(2+) dependent signal.
前列腺癌是导致男性癌症死亡的第二大原因。
美国。晚期疾病的唯一治疗方法是激素。
治疗,这是不能治愈的。激素治疗受到严重限制
因为雄激素依赖型肿瘤通常会变成雄激素非依赖型
尽管在监管方面已经做了大量的工作
雄激素作用下的前列腺细胞生长及其相关分子事件
雄激素撤退,对受体知之甚少
由雄激素非依赖性前列腺癌细胞表达。我们一直在
通过以下途径研究治疗这种肿瘤的新方法
新的细胞表面受体的鉴定
激活磷脂酰肌醇信号的抑制信号
通过激活磷脂酰肌醇信号转导通路
和细胞内钙离子的动员。十二种激素和
神经递质刺激心肌细胞内游离钙离子浓度升高
人雄激素非依赖性前列腺癌细胞系。刺激
腺嘌呤核苷酸的质膜受体,P2嘌呤能
受体持续引起Ca(2+)释放大量增加,接近
与细胞内可释放的钙离子总量之比。钙离子通道的研究
阻滞剂和EGTA表明,这种反应产生了大约50%。
从内部门店发布,50%来自开业
二氢吡啶敏感的质膜钙通道。高压
磷酸肌醇异构体的高效液相色谱分析
嘌呤受体相关的磷脂酰肌醇周转率增加。治疗
用三磷酸腺苷或不可水解性类似物亚氨基二磷酸诱导的
细胞形态发生明显变化,包括染色质凝聚和
核仁变性,并在体外显著抑制细胞生长。
正常前列腺细胞被触发经历程序性细胞死亡
对雄激素停用的反应。这种反应可被Ca(2+)抑制
通道阻滞剂。我们的数据表明,或许有可能绕过
雄激素非依赖性前列腺中雄激素受体的缺失
癌细胞,并通过激活一种细胞毒性反应
Ca(2+)依赖信号。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('J B TREPEL', 18)}}的其他基金
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
信号转导事件和细胞生长的调节
- 批准号:
5201306 - 财政年份:
- 资助金额:
-- - 项目类别:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
信号转导事件和细胞生长的调节
- 批准号:
3838098 - 财政年份:
- 资助金额:
-- - 项目类别:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
信号转导事件和细胞生长的调节
- 批准号:
3752385 - 财政年份:
- 资助金额:
-- - 项目类别:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
信号转导事件和细胞生长的调节
- 批准号:
6163303 - 财政年份:
- 资助金额:
-- - 项目类别:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
信号转导事件和细胞生长的调节
- 批准号:
3774615 - 财政年份:
- 资助金额:
-- - 项目类别:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
信号转导事件和细胞生长的调节
- 批准号:
3853226 - 财政年份:
- 资助金额:
-- - 项目类别:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
信号转导事件和细胞生长的调节
- 批准号:
6123681 - 财政年份:
- 资助金额:
-- - 项目类别:
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