SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
批准号:
3853226
负责人:
J B TREPEL
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
DiGeorge's syndrome androgen receptor antineoplastic antibiotics biological signal transduction biomarker calcium flux cell differentiation cell growth regulation clone cells gene expression hormone related neoplasm /cancer human tissue neoplastic cell neoplastic growth neuroendocrine system phospholipase C prostate neoplasms purine /pyrimidine metabolism receptor coupling transforming growth factors
中文摘要
这个项目旨在增加我们对生物学的理解
英文摘要
This project is designed to increase our understanding of the biology of
prostate cancer and to develop a new approach to the treatment of
advanced prostatic cancer through the study of the signal transduction
events regulating the growth of human prostate carcinoma cell lines.
This work is currently focused on (1) effects of cAMP on growth and
differentiation, and (2) cytotoxicity through activation of P2-
purinergic receptors. We found that elevation of intracellular cAMP is
highly growth-inhibitory to all prostate carcinoma cell lines tested,
and induces neuronal morphology in two of four cell lines. All of the
cell lines expressed one or more markers of neuroendocrine
differentiation, including dense core granules, NSE, S100, and
neurofilament proteins. In collaboration with the Molecular Oncology
Group, CPB, we tested for the expression and activity of the
neuroendocrine marker pp60c-src and found high levels of src kinase
activity that were increased after cAMP treatment. In collaboration
with the Tumor Cell Biology Section, CPB, we found that two ansamycin
antibiotics reported to inhibit src activity were highly potent
cytotoxic agents in all prostatic carcinoma cell lines. Studies of the
mechanism of cAMP-induced growth inhibition demonstrated that cAMP
induces the secretion of bioactive TGF-Beta2, an increase in TGF-Beta2
transcription, and activation of cAMP response elements in the TGF-Beta2
promoter. P2-purinergic receptor studies demonstrated that
androgen-independent prostate carcinoma cell lines express P2-purinergic
receptors that are coupled to phospholipase C activation, acute Ca+
mobilization, the induction of prolonged Ca2+ oscillations, growth
arrest, and cell death. In the androgen-sensitive cell line LNCaP,
however, P2 agonists did not stimulate phospholipase C activity, did not
induce Ca2+ release, and did not inhibit growth, while both cell types
expressed specific P2 receptors, with comparable Kd and Bmax, These data
strongly implicate phospholipase C activation and prolonged Ca2+
mobilization in the growth-inhibitory and cytotoxic effect of
P2-purinergic receptor agonists.
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SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
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批准号:5201306
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
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批准号:3838098
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
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批准号:3752385
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
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批准号:6163303
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
ANALYSIS OF DRUG RESISTANCE BY FLOW MICROFLUOROCYTOMETRY
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批准号:3874461
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
ANALYSIS OF DRUG RESISTANCE BY FLOW MICROFLUOROCYTOMETRY
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批准号:3774616
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
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批准号:3774615
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
ANALYSIS OF DRUG RESISTANCE BY FLOW MICROFLUOROCYTOMETRY
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批准号:3896333
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
SIGNAL TRANSDUCTION EVENTS AND HE REGULATION OF CELL GROWTH
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批准号:3874460
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
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批准号:6123681
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
SIGNAL TRANSDUCTION EVENTS AND THE REGULATION OF CELL GROWTH
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批准号:2464465
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
ANALYSIS OF DRUG RESISTANCE BY FLOW MICROFLUOROCYTOMETRY
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批准号:3838099
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J B TREPEL
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依托单位:
海外基金