IGF and IGF Receptor Function in Mammary Development
IGF 和 IGF 受体在乳腺发育中的功能
基本信息
- 批准号:8136164
- 负责人:
- 金额:$ 30.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-03-01 至 2013-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffinityAlveolarBindingBreast Cancer CellCell Cycle ProgressionComplexDataDevelopmentDominant-Negative MutationDuctalEGF geneEpithelialEpithelial CellsFatty acid glycerol estersFundingGeneticGoalsGrowthHumanHybridsIn VitroIncidenceInsulinInsulin ReceptorInsulin-Like Growth Factor IInsulin-Like Growth Factor IIInsulin-Like Growth Factor ReceptorLaboratoriesLactationLigandsMammary NeoplasmsMammary glandMediatingMediator of activation proteinNormal tissue morphologyPathway interactionsPatternPregnancyProlactin ReceptorProtein IsoformsPubertyRNA SplicingReceptor SignalingResearchRoleSignal PathwaySignal TransductionSpecificityStagingTestingTissuesTransgenic OrganismsVariantWood materialbasecancer typefactor Cin vivomalignant breast neoplasmmammary epitheliumpostnatalpublic health relevancereceptorreceptor expressionreceptor functionresearch studytranscription factor
项目摘要
DESCRIPTION (provided by applicant): The IGF ligands, IGF-I and IGF-II, and the IGF type I receptor (IGF-IR) have demonstrated roles in growth of mammary epithelium during normal development. Moreover, the IGFs and IGF-IR promote proliferation of breast cancer cells and are implicated in incidence and growth of breast cancers. Our previous studies demonstrated that IGF-I and IGF-II are distinctly expressed during pubertal and pregnancy-induced development of the mammary epithelium. During the previous funding period, we demonstrated that IGF-I regulates cell cycle progression in mammary epithelial cells and showed unique roles for IGF-I expressed in epithelial and stromal compartments of the developing mammary gland. We further elucidated how patterning of IGF-II expression is regulated in the mammary epithelium. Recent data suggest that the IGF ligands can signal through heterodimers of the IGF-IR and the insulin receptor (IR) in addition to homodimers of the IGF-IR. Moreover, a splice variant of the IR known as the IR-A isoform, has high specificity for IGF-II but not IGF-I. Our preliminary data show that mammary specific deletion of the IR during alveolar differentiation results in significant disruption of alveolar development and lactation. Furthermore, analysis of receptor expression suggests that the ratio of the two IR isoforms varies in mammary epithelial cells during pregnancy and lactation and that a significant portion of the IGF-IR exists as a hybrid receptor with the IR in mammary epithelial cells. Thus, the goal of the experiments proposed in this application is to test the hypothesis that the different IGF signaling receptors have distinct functions in alveolar differentiation and lactation. To test this hypothesis, we propose both in vitro experiments and in vivo transgenic studies to activate or disrupt signaling through the IRs, IGF-IR and hybrid receptors in mammary epithelial cells.
Public Health Relevance Statement: The results of the proposed experiments will elucidate IGF receptor-specific actions and downstream signaling pathways in proliferation, survival and differentiation of normal mammary epithelial cells. These studies will also have important implications for the roles of these receptors and pathways in breast cancers.
描述(由申请方提供):已证实IGF配体、IGF-I和IGF-II以及IGF I型受体(IGF-IR)在正常发育期间的乳腺上皮生长中发挥作用。此外,IGFs和IGF-IR促进乳腺癌细胞的增殖,并与乳腺癌的发生和生长有关。我们以前的研究表明,IGF-I和IGF-II在青春期和妊娠诱导的乳腺上皮发育过程中有不同的表达。在之前的资助期间,我们证明了IGF-I调节乳腺上皮细胞的细胞周期进程,并显示了IGF-I在发育中的乳腺上皮和基质区室中表达的独特作用。我们进一步阐明了IGF-II表达的模式是如何在乳腺上皮中调节的。最近的数据表明,除了IGF-IR的同源二聚体之外,IGF配体还可以通过IGF-IR和胰岛素受体(IR)的异源二聚体进行信号传导。我们的初步数据表明,乳腺特异性删除的IR在肺泡分化的结果在肺泡发育和泌乳的显着中断。此外,受体表达的分析表明,两个IR亚型的比例在乳腺上皮细胞在怀孕和哺乳期间变化,并且IGF-IR的显著部分作为与IR的混合受体存在于乳腺上皮细胞中。因此,本申请中提出的实验的目的是检验不同IGF信号传导受体在肺泡分化和泌乳中具有不同功能的假设。为了验证这一假设,我们提出了体外实验和体内转基因研究,以激活或破坏信号通过IR,IGF-IR和杂交受体在乳腺上皮细胞。
公共卫生相关性声明:实验结果将阐明IGF受体在正常乳腺上皮细胞增殖、存活和分化中的特异性作用和下游信号通路。这些研究也将对这些受体和途径在乳腺癌中的作用产生重要影响。
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)
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Teresa L Wood其他文献
Teresa L Wood的其他文献
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{{ truncateString('Teresa L Wood', 18)}}的其他基金
Pathways that regulate basal and metastatic phenotypes in triple negative breast cancers
调节三阴性乳腺癌基础表型和转移表型的途径
- 批准号:
10059304 - 财政年份:2017
- 资助金额:
$ 30.18万 - 项目类别:
Pathways that regulate basal and metastatic phenotypes in triple negative breast cancers
调节三阴性乳腺癌基础表型和转移表型的途径
- 批准号:
9246896 - 财政年份:2017
- 资助金额:
$ 30.18万 - 项目类别:
2013, 2014 and 2015 Mammary Gland Biology Gordon Research Conference & Gordon Res
2013年、2014年和2015年乳腺生物学戈登研究会议
- 批准号:
8526013 - 财政年份:2013
- 资助金额:
$ 30.18万 - 项目类别:
IGF and IGF Receptor Function in Mammary Development
IGF 和 IGF 受体在乳腺发育中的功能
- 批准号:
8036817 - 财政年份:2010
- 资助金额:
$ 30.18万 - 项目类别:
Nestin: A Putative Marker of a Mammary Stem and Progenitor Cell Lineage
巢蛋白:乳腺干细胞和祖细胞谱系的假定标记
- 批准号:
7230129 - 财政年份:2006
- 资助金额:
$ 30.18万 - 项目类别:
Nestin: A Putative Marker of a Mammary Stem and Progenitor Cell Lineage
巢蛋白:乳腺干细胞和祖细胞谱系的假定标记
- 批准号:
7082282 - 财政年份:2006
- 资助金额:
$ 30.18万 - 项目类别:
Mechanisms of Death and Survival in Oligodendroglia
少突胶质细胞的死亡和生存机制
- 批准号:
7628361 - 财政年份:2005
- 资助金额:
$ 30.18万 - 项目类别:
Mechanisms of Death and Survival in Oligodendroglia
少突胶质细胞的死亡和生存机制
- 批准号:
7450794 - 财政年份:2005
- 资助金额:
$ 30.18万 - 项目类别:
Mechanisms of Death and Survival in Oligodendroglia
少突胶质细胞的死亡和生存机制
- 批准号:
7254073 - 财政年份:2005
- 资助金额:
$ 30.18万 - 项目类别:
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