Neuroendocrine Cells in Prostate Cancer
前列腺癌中的神经内分泌细胞
基本信息
- 批准号:7728880
- 负责人:
- 金额:$ 19.96万
- 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:2008-08-01 至 2010-07-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAdhesionsAgonistAndrogen ReceptorAndrogensAnimalsApoptosisApoptoticBiological AssayBioluminescenceBombesinCalcitoninCardiacCaspaseCastrationCatalytic DomainCell LineCellsChronicClinical TreatmentClinical TrialsConditioned Culture MediaDataDependenceDiagnostic radiologic examinationDiseaseEGF geneEngineeringEnvironmentEpidermal Growth Factor ReceptorExhibitsFamily memberFrequenciesG-Protein-Coupled ReceptorsGoalsGrowthHormonesHumanImageImmunohistochemistryIn Situ Nick-End LabelingInvasiveKnowledgeLNCaPLeftLinkLiteratureLuciferasesMalignant Epithelial CellMalignant NeoplasmsMalignant neoplasm of prostateMediatingMitogen-Activated Protein KinasesMitoticModalityModelingNeoplasm MetastasisNeuroendocrine CellNeuropeptidesNeurosecretory SystemsNeurotensinNude MicePatientsPeptidesPhenotypePhosphorylationPhosphotransferasesPhysiciansPhysiologyProcessProliferatingPropertyProstateProstatic NeoplasmsRateReportingRoleRouteSRC geneSamplingSerotoninSignal PathwaySignal TransductionSiteSourceStagingStaining methodStainsStimulation of Cell ProliferationTestingTherapeuticTimeTumor-DerivedTyrosine PhosphorylationWestern BlottingWound HealingXenograft ModelXenograft procedureandrogen independent prostate cancerannexin A5autocrinebasecancer cellcell growthhuman diseaseimplantationin vivoinhibitor/antagonistinsightleukemiamalignant breast neoplasmmigrationmouse modelmutantneoplastic cellnovelnovel therapeuticsoutcome forecastparacrineparathyroid hormone-related proteinreceptorresponsesizesuccesstherapeutic targettissue culturetumortumor progression
项目摘要
Cells with neuroendocrine (NE)-like properties have been implicated in progression of prostate cancer to hormone
independence and increased aggressiveness. NE-like cells are postulated to promote the survival, growth, and
metastatic capabilities of surrounding tumor cells by secreting factors that promote these processes, particularly in
an androgen-depleted environment. In a nude mouse xenograft model, we tested this paracrine hypothesis and
showed that artificially engineered NE-like LNCaP cells provide a growth advantage to non-engineered LNCaP
tumor cells following castration (androgen ablation), as compared to LNCaP tumor cells lacking such NE cells
upon inoculation. However, the mechanism of action of the NE-like cells in this assay is unknown, i.e., whether
they promote mitogenesis, survival, or metastases. We propose to study these various possibilities in the nude
mouse model we have established by examining tumors that arise following castration from various combinations
of NE-like cells and parental LNCaP cells for markers of apoptosis (caspase activation, TUNEL, annexin V, etc.),
proliferation (Ki67, MAP kinase activation, STAT tyrosine phosphorylation, etc.), metastases, or ability to exhibit
enhanced growth following re-implantation either with or without castration. The relevance of these findings will
be assessed in human tumors by immunohistochemical staining of each marker in samples from patients of
various treatment and clinical modalities. In addition, we will investigate the signaling pathways stimulated by the
secreted products of NE-like cells. Most of the known secretory products of NE-like cells are agonists for G
protein coupled receptors (GPCRs). A growing literature indicates that many GPCRs transactivate and require
the EGF receptor (EGFR) (specifically phosphorylation of Tyr 845 on the EGFR by c-Src) for their action. Based
on these findings and the fact that the EGFR has been implicated as an etiological agent in prostate cancer, we
will test the dependence on the EGFR of GPCR agonists secreted by NE-like cells for inducing survival, growth
and/or metastatsis of prostate cancer cells. We also propose strategies to identify downstream effectors of EGFR
and Tyr 845 and to determine effects of Tyr 845-containing inhibitory peptides on prostate cancer growth. This
approach is hypothesized to provide a novel means of counteracting the action of NE-like cells in promoting
aggressive growth of androgen-independent prostate cancers.
具有神经内分泌(NE)样特性的细胞与前列腺癌向激素的进展有关
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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SARAH J PARSONS其他文献
SARAH J PARSONS的其他文献
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{{ truncateString('SARAH J PARSONS', 18)}}的其他基金
c-Src/EGF Receptors Interactions and Therapeutic Resistance in Breast Cancer
乳腺癌中的 c-Src/EGF 受体相互作用和治疗耐药
- 批准号:
7254940 - 财政年份:2006
- 资助金额:
$ 19.96万 - 项目类别:
c-Src/EGF Receptors Interactions and Therapeutic Resistance in Breast Cancer
乳腺癌中的 c-Src/EGF 受体相互作用和治疗耐药
- 批准号:
7629190 - 财政年份:2006
- 资助金额:
$ 19.96万 - 项目类别:
c-Src/EGF Receptors Interactions and Therapeutic Resistance in Breast Cancer
乳腺癌中的 c-Src/EGF 受体相互作用和治疗耐药
- 批准号:
7428876 - 财政年份:2006
- 资助金额:
$ 19.96万 - 项目类别:
c-Src/EGF Receptors Interactions and Therapeutic Resistance in Breast Cancer
乳腺癌中的 c-Src/EGF 受体相互作用和治疗耐药
- 批准号:
7826710 - 财政年份:2006
- 资助金额:
$ 19.96万 - 项目类别:
c-Src/EGF Receptors Interactions and Therapeutic Resistance in Breast Cancer
乳腺癌中的 c-Src/EGF 受体相互作用和治疗耐药
- 批准号:
7135324 - 财政年份:2006
- 资助金额:
$ 19.96万 - 项目类别:
c Src and EGF Receptor in Breast Cancer Development
c Src 和 EGF 受体在乳腺癌发展中的作用
- 批准号:
6690649 - 财政年份:2003
- 资助金额:
$ 19.96万 - 项目类别:
Neuroendocrine Cell Signaling in Prostate Cancer
前列腺癌中的神经内分泌细胞信号转导
- 批准号:
6563900 - 财政年份:2002
- 资助金额:
$ 19.96万 - 项目类别:
FUNCTION OF C-SRC AND RELATED KINASES IN CHROMAFFIN CELLS
C-SRC 及相关激酶在嗜铬细胞中的功能
- 批准号:
6311495 - 财政年份:2000
- 资助金额:
$ 19.96万 - 项目类别:
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