FRS2-mediated Signals in Prostatic Tumorigenesis and Development
FRS2-mediated Signals in Prostatic Tumorigenesis and Development
批准号:
7622907
负责人:
FEN WANG
金额:
$30.19万
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-07-01 至 2009-03-31
关键词:
AblationAdaptor Signaling ProteinAllelesAndrogensAnimal ModelAnimalsAttenuatedBasal CellBiochemicalBiologicalBiological AssayCancer PatientCell LineCell physiologyCellsConditionDataDevelopmentDietary ComponentEpithelialEpithelial CellsFGFR1 geneFGFR2 geneFRS2 geneFibroblast Growth FactorFibroblast Growth Factor ReceptorsFutureGenetically Engineered MouseHealthHealth BenefitHealthcare SystemsHomeostasisInterruptionLifeLife ExpectancyLightLinkMalignant NeoplasmsMalignant neoplasm of prostateMediatingModelingMolecularMorphogenesisNatural regenerationPhosphotransferasesPlayPopulationPrevention interventionPrevention strategyProcessProstateProstate Cancer therapyProstaticProstatic NeoplasmsProstatic hypertrophyProtein IsoformsProtein Tyrosine KinaseQuality of lifeReceptor Protein-Tyrosine KinasesReceptor SignalingRegulationRoleSignal PathwaySignal TransductionSocietiesStem cellsSystems AnalysisTechnologyTestingTissuesTumor EscapeTumorigenicitybasecancer celldesignhuman FRS2 proteinimprovedin vivoneoplastic cellnovelnutritionprecursor cellpreventreceptortooltumortumor initiationtumor progressiontumorigenesis
中文摘要
摘要
多效性成纤维细胞生长因子(成纤维细胞生长因子)控制广泛的细胞过程,包括
通过激活四个高度同源的成纤维细胞生长因子受体,实现前列腺的发育、功能和动态平衡
(FGFR)跨膜酪氨酸激酶。成纤维细胞生长因子信号轴的异常表达和激活
常被发现与前列腺癌的发生和发展有关。FRS2a是一种连接接头蛋白
FGFR激活下游信号转导靶点,由FGFR1和FGFR1差异磷酸化
前列腺上皮细胞中的FGFR2激酶。FRS2a在发育中的前列腺中动态表达,这是
与前列腺分支形态发生、雄激素诱导的再生和肿瘤的发生有关。这个
项目是测试FGFR异构体特异性激活FRS2a介导的信号发挥作用的假设
前列腺上皮细胞增殖分化调控中的重要作用
FRS2a介导的信号异常激活与前列腺的发育和再生有关
肿瘤发生,这是根据我们最近的发现制定的。努力的重点将是利用基因
转基因小鼠以及分子生物学、细胞生物学和生化技术
异常细胞信号如何在前列腺癌的发生和发展中起作用。具体目标是
描述FRS2a的结构域,这些结构域对于介导FGFR信号很重要;为了表征FRS2a的结构域
FRS2在前列腺发育和组织动态平衡中的作用;并研究异常信号如何
FRS2a在前列腺癌的发生、发展中起重要作用。我们的目标是
了解FGFR如何在底物水平诱导受体特异性信号以及FRS2a介导的作用
前列腺发育、组织动态平衡和肿瘤发生的信号。理解FGFR的作用
前列腺发育和肿瘤发生中的信号将为设计新的治疗策略提供新的线索
前列腺癌发生和发展的未来预防和阻断。动物模型
该项目的开发不仅将为进一步研究前列腺癌的FGFR信号提供有用的工具
开始和进展,但也用于评估营养和有效饮食成分在
前列腺癌进展的预防、干预和阻断。
英文摘要
Summary
The pleiotropic fibroblast growth factors (FGF) control a broad spectrum of cellular processes, including
prostate development, function, and homeostasis, by activating the four highly homologous FGF receptor
(FGFR) transmembrane tyrosine kinases. Aberrant expression and activation of the FGF signaling axis are
often found associated with prostatic tumor development and progression. FRS2a is an adaptor protein linking
the FGFR kinases to downstream signaling targets, which is differentially phosphorylated by the FGFR1 and
FGFR2 kinases in prostate epithelial cells. FRS2a is dynamically expressed in developing prostates, which is
associated with prostatic branching morphogenesis, androgen-induced regeneration, and tumorigenesis. The
project is to test the hypothesis that FGFR isoform-specific activation of FRS2a-mediated signals play
important roles in regulating proliferation and differentiation of precursor cells for prostatic epithelial cells during
development and regeneration, and aberrant activation of FRS2a-mediated signaling contributes to prostatic
tumorigenesis, which was formulated based on our recent findings. Efforts will be focused on using genetically
engineered mouse as well as molecular biological, cell biological, and biochemical technologies to understand
how aberrant cell signaling contributes to prostate tumor initiation and progression. The specific aims are to
characterize the structural domain of FRS2a that are important for mediating FGFR signals; to characterize the
role of FRS2 in prostatic development and tissue homeostasis; and to investigate how aberrant signals
mediated by FRS2a contribute to prostatic tumorigenesis and tumor progression. The objective is to
understand how FGFR elicits receptor specific signals at the substrate level and the roles of FRS2a-mediated
signals in prostatic development, tissue homeostasis, and tumorigenesis. Understanding the role of FGFR
signals in prostatic development and tumorigenesis will shed new light on designing new strategies for
prevention and interception of prostate cancer initiation and progression in the future. Animal models
developed in the project will provide a useful tool not only for further studying FGFR signals in prostate cancer
initiation and progression, but also for assessing the role of nutrition and active dietary components on
prevention, intervention, and interruption on prostate tumor progression.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
2014 Fibroblast Growth Factors in Development & Disease Gordon Research Conferenc
-
批准号:8648206
-
项目类别:
-
资助金额:$0.8万
-
财政年份:2014
-
负责人:FEN WANG
-
依托单位:
Fibroblast Growth Factor Signaling in Odontogenic Epithelial Stem Cells
-
批准号:8740696
-
项目类别:
-
资助金额:$28.48万
-
财政年份:2013
-
负责人:FEN WANG
-
依托单位:
Weinstein Cardiovascular Development Conference
-
批准号:8197594
-
项目类别:
-
资助金额:$2.1万
-
财政年份:2008
-
负责人:FEN WANG
-
依托单位:
Weinstein Cardiovascular Development Conference
-
批准号:7991775
-
项目类别:
-
资助金额:$2.1万
-
财政年份:2008
-
负责人:FEN WANG
-
依托单位:
Receptor-specific signaling of FGFR in the prostate
-
批准号:6610623
-
项目类别:
-
资助金额:$25.9万
-
财政年份:2003
-
负责人:FEN WANG
-
依托单位:
FRS2-mediated Signals in Prostatic Tumorigenesis and Development
-
批准号:8015334
-
项目类别:
-
资助金额:$24.7万
-
财政年份:2003
-
负责人:FEN WANG
-
依托单位:
Receptor-specific signaling of FGFR in the prostate
-
批准号:6748405
-
项目类别:
-
资助金额:$25.9万
-
财政年份:2003
-
负责人:FEN WANG
-
依托单位:
Receptor-specific signaling of FGFR in the prostate
-
批准号:7233211
-
项目类别:
-
资助金额:$24.56万
-
财政年份:2003
-
负责人:FEN WANG
-
依托单位:
FRS2-mediated Signals in Prostatic Tumorigenesis and Development
-
批准号:7652704
-
项目类别:
-
资助金额:$25.47万
-
财政年份:2003
-
负责人:FEN WANG
-
依托单位:
FRS2-mediated Signals in Prostatic Tumorigenesis and Development
-
批准号:8433519
-
项目类别:
-
资助金额:$23.22万
-
财政年份:2003
-
负责人:FEN WANG
-
依托单位:
Receptor-specific signaling of FGFR in the prostate
-
批准号:6893727
-
项目类别:
-
资助金额:$25.9万
-
财政年份:2003
-
负责人:FEN WANG
-
依托单位:
FRS2-mediated Signals in Prostatic Tumorigenesis and Development
-
批准号:7797649
-
项目类别:
-
资助金额:$25.47万
-
财政年份:2003
-
负责人:FEN WANG
-
依托单位:
Receptor-specific signaling of FGFR in the prostate
-
批准号:7074678
-
项目类别:
-
资助金额:$25.29万
-
财政年份:2003
-
负责人:FEN WANG
-
依托单位:
FRS2-mediated Signals in Prostatic Tumorigenesis and Development
-
批准号:8209723
-
项目类别:
-
资助金额:$24.7万
-
财政年份:2003
-
负责人:FEN WANG
-
依托单位: