Project 2 Fetuin-A in Prostate Cancer
项目 2 胎球蛋白-A 在前列腺癌中的应用
基本信息
- 批准号:10327934
- 负责人:
- 金额:$ 18.97万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-26 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:1-Phosphatidylinositol 3-Kinase3-DimensionalAKT Signaling PathwayAblationAddressAffectAfrican AmericanAmericanAndrogensAttenuatedBiogenesisBiological MarkersCancer EtiologyCaucasiansCellsCessation of lifeDataDeath RateDiseaseDisease OutcomeDoctor of PhilosophyEnterobacteria phage P1 Cre recombinaseFemaleFreezingGenerationsGenesGleason Grade for Prostate CancerGlycoproteinsGrowthHumanImmunohistochemistryIn VitroIndolentKnock-outKnockout MiceLNCaPLaboratoriesLeadLinear RegressionsLiverMalignant neoplasm of prostateMediatingMessenger RNAMitogen-Activated Protein KinasesModelingMolecularMusMutant Strains MiceNeoplasm MetastasisNull LymphocytesPTEN genePatient-Focused OutcomesPatientsPharmaceutical PreparationsPlayProcessProductionPrognosisPrognostic MarkerProstateProstate Cancer therapyProstatic NeoplasmsProteinsProto-Oncogene Proteins c-aktPubertyRefractoryRegression AnalysisResearch PersonnelRoleSerumSignal PathwaySignal TransductionTLR4 geneThe Vanderbilt-Ingram Cancer Center at the Vanderbilt UniversityTissuesTransfectionTumor VolumeWestern BlottingXenograft procedurealpha-Fetoproteinscalcificationcancer health disparitycancer initiationcancer preventioncastration resistant prostate cancercaucasian Americancell growthcell motilityexosomeexperimental studyin vivomRNA Expressionmalemenmortalitymouse modelmutantnano-stringnanovesicleoverexpressionparticleprobasinprostate cancer cellprostate cancer cell lineprostate cancer modelprostate cancer progressiontumortumor growthtumor initiationtumor progressiontumorigenicuptake
项目摘要
PROJECT SUMMARY: FULL PROJECT 2
Even though the growth of prostate cancer (PCa) is largely driven by androgens, a subset usually develops that
is refractory to androgen ablation (also known as castration resistant PCa; CRPC) with potential for metastasis.
Preliminary data from our laboratory has implicated fetuin-A, also known as alpha 2-Heremans-Schmid
glycoprotein (AHSG), in the growth of PCa cells and in the production of “uptake-competent” exosomes. The
objective of the proposed studies is to define the role and significance of fetuin-A in prostate cancer progression.
We hypothesize that PCa cells express ectopic fetuin-A which is secreted and taken up by the cells via TLR4 to
mediate the biogenesis of `uptake-competent' exosomes that promote PCa growth via activation of pAKT/pERK;
moreover, we postulate that elevated fetuin-A expression serves as a prognostic biomarker for PCa. Three
specific aims are proposed: Aim 1. To determine if fetuin-A expression is higher in AA PCa tissues relative
to Caucasian American (CA) PCa tissues and whether high fetuin-A expression is associated with high
Gleason Scores (>6) and enhanced pAKT and pERK. We will analyze mRNA expression of fetuin-A using
NanoString as well as pAKT/pERK protein levels using immunohistochemistry (IHC) analysis of human PCa
tissues. Multivariable linear regression analysis will be used to determine the correlation between fetuin-A, pAKT,
pERK and Gleason scores in PCa tissues of AA and CA patients, as well as other progression parameters such
as positive margins and spread of PCa. It is expected that fetuin-A, pAKT and pERK will be expressed at high
levels in PCa tissues of AA patients particularly those with high Gleason scores (>6). Aim 2. To determine the
role of ectopic fetuin-A in exosome biogenesis, promotion of 2-D and 3-D growth, motility and invasive
capacity of PCa cells. In this aim, we will overexpress and knockout fetuin-A in two PCa cell lines to determine
whether fetuin-A plays a causal role in the biogenesis of `uptake competent' exosomes that transmit growth
signals in recipient cells. We expect to demonstrate that exosomes from fetuin-A overexpressing cells will
promote 2-D, 3-D growth and motility and invasion of PCa cells while exosomes from fetuin-A null cells will not.
Aim 3. To investigate the efficacy of targeting fetuin-A mediated signaling on the suppression of prostate
tumor initiation and growth in mice. In this aim, we will utilize the Pten-null mouse model for PCa to determine
whether Pten loss requires intact fetuin-A gene to mediate its tumorigenic role and whether loss of fetuin-A in
Pten-/-/fetuin-A-/- double mutant mice attenuates the tumorigenic role of Pten-null. We expect reduced tumor
growth in the double mutant mice compared to Pten-null fetuin-A+/+ mice. Significance: There is an urgent need
to identify biomarkers that can differentiate CRPC from indolent PCa and this proposal addresses that need and
evaluates the process by which fetuin-A enhances PCa tumor growth.
项目概要:完整项目2
尽管前列腺癌(PCa)的生长在很大程度上是由雄激素驱动的,但一部分通常会发展为
雄激素消融(也称为去势抵抗性PCa; CRPC)难治,并有转移的可能。
我们实验室的初步数据表明,胎球蛋白A,也称为α 2-赫尔曼-施密德
在PCa细胞的生长和“摄取能力”外泌体的产生中,蛋白质是糖蛋白(AHSG)的主要成分。的
所提出的研究的目的是确定胎球蛋白-A在前列腺癌进展中的作用和意义。
我们假设PCa细胞表达异位胎球蛋白-A,其通过TLR 4分泌并被细胞摄取,
介导通过激活pAKT/pERK促进PCa生长的“可摄取”外泌体的生物发生;
此外,我们推测升高的胎球蛋白-A表达可作为前列腺癌的预后生物标志物。三
具体目标如下:目标1。为了确定胎球蛋白-A在AA PCa组织中的表达是否相对较高,
是否高胎球蛋白-A表达与高前列腺癌相关,
Gleason评分(>6)和增强的pAKT和pERK。我们将分析胎球蛋白-A的mRNA表达,
使用人PCa的免疫组织化学(IHC)分析NanoString以及pAKT/pERK蛋白水平
组织中将使用多变量线性回归分析来确定胎球蛋白-A、pAKT、
AA和CA患者PCa组织中的pERK和Gleason评分,以及其他进展参数,
PCa的正边际和扩散。预期胎球蛋白-A、pAKT和pERK将以高水平表达,
在AA患者的PCa组织中,特别是具有高Gleason评分(>6)的那些患者的PCa水平。目标二。确定
异位胎球蛋白-A在外泌体生物发生、促进2-D和3-D生长、运动和侵袭中的作用
PCa细胞的能力。在这个目标中,我们将在两个PCa细胞系中过表达和敲除胎球蛋白-A,以确定
胎球蛋白-A是否在传递生长的“摄取能力”外泌体的生物发生中起因果作用
受体细胞中的信号。我们希望证明来自胎球蛋白-A过表达细胞的外泌体,
促进PCa细胞的2-D、3-D生长和运动以及侵袭,而来自胎球蛋白-A无效细胞的外来体则不会。
目标3。研究靶向胎球蛋白-A介导的信号转导对前列腺增生抑制的有效性,
肿瘤的发生和生长。在这个目标中,我们将利用Pten-敲除小鼠PCa模型来确定
Pten缺失是否需要完整的胎球蛋白-A基因介导其致瘤作用,
Pten-/-/胎球蛋白-A-/-双突变小鼠减弱Pten-null的致瘤作用。我们希望肿瘤缩小
与Pten缺失胎球蛋白-A +/+小鼠相比,双突变小鼠的生长。重要性:迫切需要
鉴定可以区分CRPC和惰性PCa的生物标志物,该提案解决了这一需求,
评估了胎球蛋白-A增强PCa肿瘤生长的过程。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JOSIAH OCHIENG其他文献
JOSIAH OCHIENG的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JOSIAH OCHIENG', 18)}}的其他基金
Analysis of Serum Exsomes in Patients with Colorectal and Breast Cancer
结直肠癌和乳腺癌患者血清外泌体分析
- 批准号:
8261513 - 财政年份:2011
- 资助金额:
$ 18.97万 - 项目类别:
INTEGRIN ACTIVITIES DURING TUMOR PROGRESSION BY GALECTIN-3
Galectin-3 在肿瘤进展过程中的整合素活性
- 批准号:
6485272 - 财政年份:2001
- 资助金额:
$ 18.97万 - 项目类别:
相似海外基金
REU Site: Design, Create, and Innovate 3-Dimensional User Interfaces to Improve Human Sensory and Motor Performance in Virtual Environments (HUMANS MOVE)
REU 网站:设计、创建和创新 3 维用户界面,以提高虚拟环境中的人类感官和运动表现 (HUMANS MOVE)
- 批准号:
2349771 - 财政年份:2024
- 资助金额:
$ 18.97万 - 项目类别:
Standard Grant
CAREER: Atomic-level understanding of stability and transition kinetics of 3-dimensional interfaces under irradiation
职业:对辐照下 3 维界面的稳定性和转变动力学的原子水平理解
- 批准号:
2340085 - 财政年份:2024
- 资助金额:
$ 18.97万 - 项目类别:
Continuing Grant
Artificial fabrication of 3-dimensional noncollinear magnetic order and magnetization manipulation by spin torque
三维非共线磁序的人工制造和自旋转矩磁化操纵
- 批准号:
23H00232 - 财政年份:2023
- 资助金额:
$ 18.97万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Understanding of 3-dimensional seismic behavior of RC frame high-speed railway/highway viaducts using FE analysis
使用有限元分析了解 RC 框架高速铁路/公路高架桥的 3 维抗震性能
- 批准号:
23H01489 - 财政年份:2023
- 资助金额:
$ 18.97万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Modernization of 3-dimensional printing capabilities at the Aquatic Germplasm and Genetic Resource Center
水产种质和遗传资源中心 3 维打印能力的现代化
- 批准号:
10736961 - 财政年份:2023
- 资助金额:
$ 18.97万 - 项目类别:
The 3-dimensional nest of the honey bee: organization, development, and impact on colony function
蜜蜂的 3 维巢穴:组织、发育及其对蜂群功能的影响
- 批准号:
2216835 - 财政年份:2023
- 资助金额:
$ 18.97万 - 项目类别:
Standard Grant
Research on high-density 3-dimensional polymer optical waveguide device for photonics-electronics convergence
光电子融合高密度三维聚合物光波导器件研究
- 批准号:
23H01882 - 财政年份:2023
- 资助金额:
$ 18.97万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Scaff-Net: 3 Dimensional multiphoton polymerisation printed scaffolds for medium throughput recording from stem cell derived human cortical networks.
Scaff-Net:3 维多光子聚合打印支架,用于从干细胞衍生的人类皮质网络进行中等通量记录。
- 批准号:
EP/X018385/1 - 财政年份:2023
- 资助金额:
$ 18.97万 - 项目类别:
Research Grant
3-dimensional prompt gamma imaging for online proton beam dose verification
用于在线质子束剂量验证的 3 维瞬发伽马成像
- 批准号:
10635210 - 财政年份:2023
- 资助金额:
$ 18.97万 - 项目类别:
Equipment: MRI: Track 1 Acquisition of a 3-Dimensional Nanolithography Instrument
设备:MRI:轨道 1 获取 3 维纳米光刻仪器
- 批准号:
2320636 - 财政年份:2023
- 资助金额:
$ 18.97万 - 项目类别:
Standard Grant