NERVE GROWTH FACTOR RECEPTORS & HUMAN PROSTATE NEOPLASIA
神经生长因子受体
基本信息
- 批准号:2147178
- 负责人:
- 金额:$ 16.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1993
- 资助国家:美国
- 起止时间:1993-09-30 至 1996-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Prostate neoplasia in the form of cancer and benign prostatic hyperplasia
have assumed a prominent role in the morbidity and mortality of the aging
adult male, and is projected to further increase in incidence over the
next several decades as the modal male population in North America
progressively ages. Hence, the mechanisms which regulate growth of the
prostate are of particular relevance to the management and treatment of
prostate neoplasia. In this context, paracrine interactions between
stromal cells and epithelial of the prostate are thought to play a
fundamental role in the regulation of prostate growth. Over the last few
years this laboratory has identified a novel nerve growth factor-like
protein (neurotrophin) secreted by stromal cells and a corresponding
receptor system on the adjacent epithelial cells that mediates paracrine
growth of the human prostate. Both low affinity p75 NGF receptors and
a member of the high affinity trk tyrosine kinase family of NGF receptors
occur in the human prostate. Recently, this laboratory reported that the
p75 NGF receptor is progressively lost during neoplastic progression of
the human prostate, so that it is completely absent in metastatic
prostate tumor cell lines. Since in other cell systems, the p75 receptor
is thought to modulate the activity of the trk receptors, we propose to
test the hypothesis that during neoplastic progression of the human
prostate a defect in p75 expression eliminates modulation of the trk
tyrosine kinase receptor, leading to uncontrolled growth of the prostatic
epithelial cells. In order to fully investigate the role of NGF
receptors in prostate neoplasia it is proposed to examine the immuno-
localization of the trk receptor in epithelial cells of the normal,
benign and malignant human prostate. As a follow up to these studies the
autophosphorylation of the epithelial trk receptor in response to
neurotrophin stimulation will be examined by immunoprecipitation of the
trk receptor and probing with an antiphosphotyrosine antibody.
Subsequently, the effect of growth factors not related to the
neurotrophins on NGF receptor expression is to be examined. Finally, we
will directly test the hypothesis that loss of the p75 receptor
eliminates modulation of the trk receptor leading to uncontrolled growth
of the epithelial cells by transfecting the p75 gene back into prostatic
tumor cells which we have previously demonstrated lack p75 expression.
We will then test the p75 transfectants for reduced trk auto-
phosphorylation and reduced growth rate. These studies should provide
definitive evidence for the paracrine role of neurotrophin mediated NGF
receptor signalling in the growth of the human prostate.
前列腺癌和前列腺增生
在老年人的发病率和死亡率中起着重要作用
成年男性,预计发病率将进一步增加,
在接下来的几十年里,
逐渐老化。 因此,调节细胞生长的机制
前列腺是特别相关的管理和治疗
前列腺肿瘤 在这种情况下,旁分泌之间的相互作用
前列腺的基质细胞和上皮细胞被认为是
在前列腺生长调节中的重要作用。 过去几
多年来,这个实验室已经发现了一种新的神经生长因子样
由基质细胞分泌的蛋白质(神经营养因子)和相应的
邻近上皮细胞上介导旁分泌的受体系统
人类前列腺的生长。 低亲和力p75 NGF受体和
NGF受体的高亲和力trk酪氨酸激酶家族的成员
发生在人类前列腺。 最近,该实验室报告说,
p75 NGF受体在肿瘤进展过程中逐渐丢失
人类前列腺,因此它在转移性前列腺中完全不存在,
前列腺肿瘤细胞系。 因为在其他细胞系统中,p75受体
被认为调节trk受体的活性,我们建议
测试假设,在人类肿瘤进展期间,
前列腺A中p75表达缺陷消除了trk的调节
酪氨酸激酶受体,导致前列腺的不受控制的生长
上皮细胞 为了充分研究神经生长因子的作用
受体在前列腺肿瘤中,建议检查免疫-
Trk受体在正常人上皮细胞中的定位,
良性和恶性人前列腺。 作为这些研究的后续行动,
上皮细胞trk受体的自身磷酸化
神经营养因子刺激将通过免疫沉淀法检测。
trk受体并用抗磷酸酪氨酸抗体探测。
随后,生长因子的作用与
神经营养因子对神经生长因子受体表达的影响。 最后我们
将直接检验p75受体缺失的假设
消除了导致不受控制的生长的Trk受体的调节
将p75基因导入前列腺上皮细胞,
我们先前已经证实的肿瘤细胞缺乏p75表达。
然后我们将测试p75转染子的减少的trk自动-
磷酸化和降低的生长速率。 这些研究将提供
神经营养因子介导的神经生长因子旁分泌作用的明确证据
受体信号在人类前列腺的生长。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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Daniel Djakiew其他文献
Daniel Djakiew的其他文献
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{{ truncateString('Daniel Djakiew', 18)}}的其他基金
REGULATION OF NGF EXPRESSION IN PROSTATE CANCER
前列腺癌中 NGF 表达的调节
- 批准号:
2292628 - 财政年份:1996
- 资助金额:
$ 16.39万 - 项目类别:
NERVE GROWTH FACTOR RECEPTORS & HUMAN PROSTATE NEOPLASIA
神经生长因子受体
- 批准号:
3248725 - 财政年份:1993
- 资助金额:
$ 16.39万 - 项目类别:
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