Novel effectors of ERK signaling and their potential roles in the treatment of en
ERK 信号传导的新型效应物及其在治疗 en 中的潜在作用
基本信息
- 批准号:7727351
- 负责人:
- 金额:$ 9.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-18 至 2012-08-12
- 项目状态:已结题
- 来源:
- 关键词:AccountingAntibodiesApoptosisBiological ModelsBiological Response Modifier TherapyCaenorhabditis elegansCancer BiologyCancer Cell GrowthCancer ModelCancer cell lineCell Cycle RegulationCell LineCell ProliferationCell SurvivalCellsClinicalDetectionDiagnosticDiseaseEndometrialEndometrial CarcinomaEndometriumEventFGFR2 geneHemorrhageHumanInstructionKRAS2 geneLeadMalignant Female Reproductive System NeoplasmMalignant NeoplasmsMapsMethodsMitogen-Activated Protein KinasesMitogensModelingMolecular AbnormalityMorbidity - disease rateMutationNeoplasm MetastasisOperative Surgical ProceduresOrthologous GenePathway interactionsPatientsPharmacotherapyPhosphorylationPhosphorylation SitePhosphotransferasesPlayPopulationPostmenopausePreventionProteinsRecurrent Malignant NeoplasmReproduction sporesReverse Transcriptase Polymerase Chain ReactionRoleSignal PathwaySignal TransductionSignal Transduction PathwaySmall Interfering RNAStagingSystemic diseaseTherapeuticTherapeutic InterventionTissue MicroarrayTissuesTumor Suppressor GenesUterine CancerWestern BlottingWorkangiogenesiscarcinogenesiscell growthcell motilitychemotherapyclinically relevantcohorteffective therapyextracellularfunctional genomicsglycogen synthase kinase 3 betaimprovedmortalitymultimodalityneoplasticnovelnovel strategiesnovel therapeutic interventionsmall hairpin RNAtreatment strategytumorigenesis
项目摘要
Endometrial carinoma is the most common cancer of the female reproductive tract. Most endometrial
cancers are found at an early stage and present with postmenopausal bleeding. These patients are initially
treated with comprehensive surgical staging. This treatment is often diagnostic ofthe extent of disease and
therapeutic. However, a key clinical problem in the management of patients with uterine cancers is how to
best fre¿t~ab\r¿rhced'stagieclisease ahdlhe aggressive pathoTogic histotypes that account for signficant
mortality.
Patients with high stage or recurrent cancers have systemic disease requiring novel therapeutic
interventions. Effective therapies are largely lacking. A better understanding ofthe cancer biology, such as
signal transduction pathways, will lead to new treatment strategies that will improve the survival of these
patients. Activation of the Mitogen Activating Pathway Kinase signaling pathway contributes substantially to
endometrial tumorigenesis. Our group has identified thirty novel ERK substrates through a three-part
functional genomic approach in the C. elegans model. The human orthologs of these proteins expressed in
endometrial cancer cell lines are candidate ERK substrates. Thus far, of the candidates studied, we showed
that GSK3n is important to cell growth in multiple endometrial cancer cell lines and has potential for
therapeutic interventions.. In this proposal, we will continue to characterize novel ERK candidate substrates
in endometrial cancer. In Aim 1, we will assess expression of candidate ERK1/2 substrates in the normal
endometrium, primary endometrial cancers and endometrial cancer cell lines and determine if substrate
phosphorylation is ERK-dependent. Then in aim 2, we will determine the relationship between ERK substrate
phosphorylation status and upstream ERK signaling pathway activation in primary endometrial cancers and
clinicopathologic significance of ERK substrate expression. Finally in aim 3, we will explore GSKSD
inhibition as potential therapy for endometrial cancer and assess the role of inhibiting other ERK substrates
plays in endometrial cancer cell lines. Together these studies should provide a better understanding of the
role the ERK pathway plays in endometrial carcinogenesis and may lead to improved clinical biological
therapies.
RELEVANCE (See instructions):
The work proposed will lead to both an improved understanding of endometrial cancer biology and new
approaches to the detection, prevention and treatment of uterine cancers which will result in reduced cancer
morbidity and mortality.
子宫内膜癌是女性生殖道最常见的癌症。大多数子宫内膜
项目成果
期刊论文数量(0)
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专利数量(0)
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Liang Ma其他文献
Liang Ma的其他文献
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{{ truncateString('Liang Ma', 18)}}的其他基金
Androgen and Wnt signaling in bladder cancer
膀胱癌中的雄激素和 Wnt 信号传导
- 批准号:
10727745 - 财政年份:2023
- 资助金额:
$ 9.34万 - 项目类别:
GENOME-WIDE IDENTIFICATION OF GENES REQUIRED FOR DECIDUALIZATION
蜕化所需基因的全基因组鉴定
- 批准号:
9258455 - 财政年份:2016
- 资助金额:
$ 9.34万 - 项目类别:
GENERATION OF AN INDUCIBLE SYSTEM IN THE UTERINE STROMA FOR IMPLANTATION STUDIES
用于植入研究的子宫间质中诱导系统的生成
- 批准号:
8358586 - 财政年份:2012
- 资助金额:
$ 9.34万 - 项目类别:
GENERATION OF AN INDUCIBLE SYSTEM IN THE UTERINE STROMA FOR IMPLANTATION STUDIES
用于植入研究的子宫间质中诱导系统的生成
- 批准号:
8522211 - 财政年份:2012
- 资助金额:
$ 9.34万 - 项目类别:
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