Alternative splicing and epithelial-mesenchymal plasticity in prostate tumors
前列腺肿瘤中的选择性剪接和上皮间质可塑性
基本信息
- 批准号:8196869
- 负责人:
- 金额:$ 31.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-12-01 至 2013-11-30
- 项目状态:已结题
- 来源:
- 关键词:Alternative SplicingAmerican Cancer SocietyBehaviorCellsDataDiseaseDistantEpithelialEpithelial CellsExonsFibroblast Growth Factor Receptor 2Gene ExpressionGoalsHealthHumanImageMalignant neoplasm of prostateMammalsMesenchymalMetastatic toMolecular ProfilingNeoplasm MetastasisNew YorkOutcomePatientsPrimary NeoplasmProcessPropertyProstateProstate carcinomaProstatic NeoplasmsProtein IsoformsRNA SplicingRattusRegulationReporterReportingSignal TransductionSystemTechnologyTestingTherapeuticTimeTranscriptTumor MarkersVertebratesWorkfitnessin vivokillingsmenmouse modelneoplastic cellnovelprogramstherapeutic targettumortumor progressiontumorigenesis
项目摘要
In epithelial cells alternative splicing of fibroblast growth factor receptor-2 (FGFR2) transcripts
leads to the expression of the FGFR2(IIIb) isoform, whereas in mesenchymal cells the same process
results in the synthesis of FGFR2(IIIc), which include exon IIIc. This regulated splicing is disrupted
during progression of prostate carcinomas leading to the inappropriate expression of FGFR2
isoforms. To visualize the use of FGFR2 exon IIIc in Dunning AT3 tumors in syngeneic rats we
constructed minigene constructs that report on alternative splicing. Imaging these alternative splicing
decisions revealed unexpected mesenchymal-epithelial transitions (MET) in these primary tumors.
The understanding of this epithelial-mesenchymal plasticity, revealed by differences in splicing, is the
overarching goal of this application.
To this end we propose to accomplish the following specific aims: Specific Aim 1. To
characterize the connections between FGFR2 splicing and epithelial-mesenchymal plasticity
in prostate tumors. We have developed a new bichromatic reporter that can be used to detect both
MET and epithelial-mesenchymal transitions (EMT). We have also extended our observations to well
characterized human prostate tumor cells in culture. Work accomplished in this aim will test the
hypothesis that epithelial plasticity is a general property of aggressive prostate carcinomas in
humans. Specific Aim 2. To characterize the epithelial-mesenchymal plasticity in primary
prostate tumors revealed by alterations in splicing. In this aim we will characterize the molecular
signatures and behavior of the MET clusters in primary tumors. Specific aim 3. To characterize
the connections between epithelial-mesenchymal plasticity and metastatic behavior. We will
investigate the connections between epithelial-mesenchymal plasticity and metastatic behavior.
Finally, we will isolate circulating prostate tumor cells from both the AT3 rat tumors and patients, and
we will determine their FGFR2 splicing status and their epithelial state. Work accomplished in aim
two and in this aim will test the hypothesis that epithelial-mesenchymal plasticity leads to increased
tumor fitness.
The significance of this work is twofold: First we will unravel basic information about gene
expression programs controlled by alternative splicing during prostate tumor progression. Second, the
potential significance to human health is underscored by the magnitude of prostate cancer as a health
problem. Identifying the tumors/cells that will progress to metastatic disease is a challenge and a
priority. The work proposed here should identify useful markers and perhaps even therapeutic
targets.
在上皮细胞中,成纤维细胞生长因子受体2 (FGFR2)转录物的选择性剪接
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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Mariano A. Garcia-Blanco其他文献
Protein–protein interactions and 5'-splice-site recognition in mammalian mRNA precursors
哺乳动物 mRNA 前体中的蛋白质-蛋白质相互作用和 5'-剪接位点识别
- DOI:
10.1038/368119a0 - 发表时间:
1994-03-10 - 期刊:
- 影响因子:48.500
- 作者:
Jhumku D. Kohtz;Sharon F. Jamison;Cindy L. Will;Ping Zuo;Reinhard Lührmann;Mariano A. Garcia-Blanco;James L. Manley - 通讯作者:
James L. Manley
867. Spliceosome Mediated RNA Trans-Splicing To Increase Blood Levels of Apolipoprotein A-I and High Density Lipoproteins
- DOI:
10.1016/j.ymthe.2006.08.955 - 发表时间:
2006-01-01 - 期刊:
- 影响因子:
- 作者:
Madaiah Puttaraju;Jun Wang;Alan T. Remaley;Bryan H. Brewer;Mariano A. Garcia-Blanco;Gerard J. McGarrity - 通讯作者:
Gerard J. McGarrity
868. Novel Strategies To Inhibit Ocular Neovascularization Based on Sonic Hedgehog Pathway Blockade
- DOI:
10.1016/j.ymthe.2006.08.956 - 发表时间:
2006-01-01 - 期刊:
- 影响因子:
- 作者:
Madaiah Puttaraju;Jun Wang;Alan T. Remaley;Bryan H. Brewer;Mariano A. Garcia-Blanco;Gerard J. McGarrity - 通讯作者:
Gerard J. McGarrity
Broad-spectrum antiviral ferruginol analog affects the viral proteins translation and actin remodeling during dengue virus infection
广谱抗病毒铁醇类似物影响登革热病毒感染期间的病毒蛋白翻译和肌动蛋白重塑
- DOI:
10.1016/j.antiviral.2025.106139 - 发表时间:
2025-05-01 - 期刊:
- 影响因子:4.000
- 作者:
Vicky C. Roa-Linares;Liliana A. Betancur-Galvis;Miguel A. González-Cardenete;Mariano A. Garcia-Blanco;Juan C. Gallego-Gomez - 通讯作者:
Juan C. Gallego-Gomez
Host RNA-binding proteins and specialized viral RNA translation mechanisms: Potential antiviral targets
宿主 RNA 结合蛋白和专门的病毒 RNA 翻译机制:潜在的抗病毒靶点
- DOI:
10.1016/j.antiviral.2025.106142 - 发表时间:
2025-05-01 - 期刊:
- 影响因子:4.000
- 作者:
Leandro Fernández-García;Mariano A. Garcia-Blanco - 通讯作者:
Mariano A. Garcia-Blanco
Mariano A. Garcia-Blanco的其他文献
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{{ truncateString('Mariano A. Garcia-Blanco', 18)}}的其他基金
Research Project 2: Role of Posttranscriptional Regulatory Networks in the Pathogenesis of Ebola Virus Disease
研究项目2:转录后调控网络在埃博拉病毒疾病发病机制中的作用
- 批准号:
10188760 - 财政年份:2021
- 资助金额:
$ 31.4万 - 项目类别:
Research Project 2: Role of Posttranscriptional Regulatory Networks in the Pathogenesis of Ebola Virus Disease
研究项目2:转录后调控网络在埃博拉病毒疾病发病机制中的作用
- 批准号:
10602493 - 财政年份:2021
- 资助金额:
$ 31.4万 - 项目类别:
Research Project 2: Role of Posttranscriptional Regulatory Networks in the Pathogenesis of Ebola Virus Disease
研究项目2:转录后调控网络在埃博拉病毒疾病发病机制中的作用
- 批准号:
10394321 - 财政年份:2021
- 资助金额:
$ 31.4万 - 项目类别:
Consequences and mechanism of aberrant splicing in African American prostate cancer disparities
非裔美国人前列腺癌差异中异常剪接的后果和机制
- 批准号:
9884534 - 财政年份:2017
- 资助金额:
$ 31.4万 - 项目类别:
Consequences and mechanism of aberrant splicing in African American prostate cancer disparities
非裔美国人前列腺癌差异中异常剪接的后果和机制
- 批准号:
10116165 - 财政年份:2017
- 资助金额:
$ 31.4万 - 项目类别:
Fourth Pan American Dengue Research Network Meeting
第四届泛美登革热研究网络会议
- 批准号:
8836790 - 财政年份:2014
- 资助金额:
$ 31.4万 - 项目类别:
Targeting host 3'-5' exonucleases required for flaviviral infection
靶向黄病毒感染所需的宿主 3-5 核酸外切酶
- 批准号:
8540496 - 财政年份:2012
- 资助金额:
$ 31.4万 - 项目类别:
IsoCyte Laser Scanning Plate Cytometer for High-throughput, High-content Assays
IsoCyte 激光扫描板细胞仪用于高通量、高内涵分析
- 批准号:
8052318 - 财政年份:2011
- 资助金额:
$ 31.4万 - 项目类别:
Alternative splicing and epithelial-mesenchymal plasticity in prostate tumors
前列腺肿瘤中的选择性剪接和上皮间质可塑性
- 批准号:
7991827 - 财政年份:2008
- 资助金额:
$ 31.4万 - 项目类别:
Integrated instrument system for maintenance and delivery of RNAi libraries
用于维护和交付 RNAi 文库的集成仪器系统
- 批准号:
7388756 - 财政年份:2008
- 资助金额:
$ 31.4万 - 项目类别:
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