Characterization of zinc dysregulation in normal and cancerous prostate cells.
正常和癌性前列腺细胞中锌失调的特征。
基本信息
- 批准号:8063345
- 负责人:
- 金额:$ 4.18万
- 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:2011-01-01 至 2012-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAlzheimer&aposs DiseaseAreaBindingCancerousCell LineCell NucleusCell physiologyCellsComplementCuesCytosolDataDiseaseDisease ProgressionEndoplasmic ReticulumEnzymesExhibitsFluorescence MicroscopyGoalsHomeostasisHuman bodyHuntington DiseaseImmunofluorescence MicroscopyIndividualInositolIonsKnowledgeLeadLifeLocationMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of prostateMapsMeasuresMessenger RNAMetalsMitochondriaMolecularMonitorMovementOrganellesPathologyPathway interactionsPhysiologicalPlayProstateProteinsReceptor SignalingResearchResolutionReverse Transcriptase Polymerase Chain ReactionRoentgen RaysRoleSecretory VesiclesSignal TransductionStressSubcellular FractionsSynchrotronsTechniquesTissuesTrace ElementsTransition ElementsVCaPVesicleWestern BlottingWorkZincbasecancer cellcell fixingcellular imagingresearch studyresponsesensortooltranscription factor MTF-1tripolyphosphatezinc-binding protein
项目摘要
DESCRIPTION (provided by applicant): Zinc is an important trace element that is found throughout the human body and functions in structural and catalytic activities. It is the second most abundant transition metal in the body. The highest concentration of Zn+2 is found in the prostate gland. While normal prostate cells have exceptionally high Zn+2 levels it is markedly depleted in prostate cancer. It is not yet clear if Zn+2 reduction is a cause or consequence of prostate cancer but it is important to understand the differences in Zn+2 distribution between noncancerous and cancer cells. The overall goal of this research is to define differences in Zn+2 pools between noncancerous and cancerous prostate cells and correlate these changes with proteins that regulate Zn2+ homeostasis. Because Zn+2 is markedly reduced in prostate cancer we would like elucidate where in the cell Zn+2 is reduced. Cells have the ability to store labile Zn+2 in secretory vesicles and are able to mobilize this metal in response to certain cellular cues, such as stresses or cellular signals. This study aims to reveal the difference in Zn+2 distributions at the subcellular level in noncancerous compared to cancerous cells. The goal is to define the physiological role of Zn+2, as well as determine whether Zn+2 reduction plays a role in the pathology of prostate cancer. This proposal has two specific aims (1) characterize changes in expression levels and/or localization of proteins responsible for controlling Zn2+ homeostasis; (2) elucidate the Zn+2 pools in noncancerous and cancerous cell lines using genetically encoded sensors targeted to different compartment of the cell. These live cell studies will be complemented by x-ray fluorescence microscopy on fixed cells to map total Zn+2 and ICP-MS on subcellular fractions.
PUBLIC HEALTH RELEVANCE: Live cell imaging of Zn+2 ions in noncancerous and cancerous prostate cells will greatly enhance our knowledge on how this metal is dysregulated when normal prostate cells become malignant. The tools developed in this work can be targeted to different compartments of the cells to obtain quantitative levels of Zn+2 within individual organelles. Obtaining quantitative Zn+2 levels in different compartments will open new areas of research to investigate what proteins are involved in Zn+2 binding and cellular signals.
描述(由申请人提供):锌是一种重要的微量元素,存在于人体各处,具有结构和催化活性。它是人体内第二丰富的过渡金属。锌离子浓度最高的部位是前列腺。虽然正常的前列腺细胞有异常高的锌+2水平,但它在前列腺癌中明显减少。目前尚不清楚Zn+2的减少是前列腺癌的原因还是结果,但了解非癌细胞和癌细胞之间Zn+2分布的差异是很重要的。本研究的总体目标是确定非癌和癌前列腺细胞中Zn+2池的差异,并将这些变化与调节Zn2+稳态的蛋白质联系起来。因为锌+2在前列腺癌中显著减少我们想要阐明细胞中锌+2减少的位置。细胞有能力将不稳定的锌+2储存在分泌囊泡中,并能够根据某些细胞信号(如压力或细胞信号)调动这种金属。本研究旨在揭示非癌细胞与癌细胞在亚细胞水平上Zn+2分布的差异。目的是明确Zn+2的生理作用,并确定Zn+2还原是否在前列腺癌病理中起作用。该提议有两个具体目的:(1)表征负责控制Zn2+稳态的蛋白的表达水平和/或定位的变化;(2)利用针对细胞不同区室的基因编码传感器阐明非癌和癌细胞系中的Zn+2池。这些活细胞研究将通过固定细胞上的x射线荧光显微镜进行补充,以绘制总Zn+2和亚细胞部分的ICP-MS。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Jose Guadalupe Miranda其他文献
Jose Guadalupe Miranda的其他文献
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{{ truncateString('Jose Guadalupe Miranda', 18)}}的其他基金
Characterization of zinc dysregulation in normal and cancerous prostate cells.
正常和癌性前列腺细胞中锌失调的特征。
- 批准号:
8260775 - 财政年份:2011
- 资助金额:
$ 4.18万 - 项目类别: