Role of EFEMP1 in the Pathogenesis of Leiomyoma
EFEMP1 在平滑肌瘤发病机制中的作用
基本信息
- 批准号:9351192
- 负责人:
- 金额:$ 0.83万
- 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:2009-08-15 至
- 项目状态:未结题
- 来源:
- 关键词:AccountingAfrican AmericanAgeAnemiaBenignBiologyCell ProliferationCellsCellular MorphologyColorectal CancerDNADNA MethylationDNA methyltransferase inhibitionDataDeoxycytidineDown-RegulationEndometrial CarcinomaEpidermal Growth FactorEpigenetic ProcessExtracellular MatrixFamilyFunctional disorderGene ExpressionGenesGlycoproteinsGrowthGrowth and Development functionGynecologyHealth Care CostsHumanHypermethylationHysterectomyInfertilityInstructionLeiomyomaMalignant NeoplasmsMalignant neoplasm of lungMalignant neoplasm of prostateModificationMolecularMorbidity - disease rateMyometrialNatureNormal tissue morphologyOne-Step dentin bonding systemOrganogenesisOutputPathogenesisPathway interactionsPatternPelvic PainPhenotypePilot ProjectsPlayPrevalencePreventive InterventionProductionProteinsPublic HealthPublishingRegulationResearchRoleS1-5 proteinSignal TransductionSmooth Muscle MyocytesSymptomsSystemTestingTherapeutic InterventionTimeTissuesTumor Suppressor ProteinsUnited StatesUnited States National Institutes of HealthUterine FibroidsUterine NeoplasmsUterine hemorrhageWomanagedangiogenesisbasecell growthdifferential expressionexperimental studyfibulinknock-downmyometriumoverexpressionprogramsreproductivetumortumor growthtumorigenesis
项目摘要
Leiomyomas are highly pervasive benign tumors of the uterus that have an overall prevalence of 70% in
women by the age of 50. They are the leading cause of hysterectomy in the United States, accounting for
almost 50% of the 600,000 hysterectomies performed annually and $34 billion dollars in annual healthcare
costs. Despite their prevelance and public health impact, the cellular and molecular mechanisms regulating the
development and growth of leiomyoma are not well understood. Phenotypically, these tumors are distinct
from the adjacent normal tissue largely due to the overproduction of extracellular matrix component. We and
others have demonstrated that amongst the differentially expressed genes between LEIO and MYO, is
EFEMP1, suggesting a role in the pathogenesis of these tumors. Among the 20 most differentially expressed
genes, we identified Epidermal-growth factor-containing fibulin-like extracellular matrix 1 (EFEMP1). EFEMP1
encodes one of the fibulins (fibulin-3; FBLN3), a family of extracellular matrix glycoproteins that has been
demonstrated to play roles in angiogenesis, extracellular matrix production, organogenesis, and cell
morphology and growth. Differential expression of EFEMP1 has been implicated in tumor growth,
angiogenesis, and extracellular matrix production in a number of malignancies. Specifically, the downregulation
of EFEMP1 has been demonstrated to promote growth and altered intracellular signaling in prostate, lung,
endometrial, and colorectal cancer. Neither the expression pattern nor the role of EFEMP1 and its protein
product have been investigated in leiomyomas. Our lab has generated preliminary data that demonstrate
that EFEMP1 is markedly downregulated in leiomyomas. Based on its role as a tumor suppressor in various
cancers, we hypothesize that aberrant expression of EFEMP1 contributes to the pathophysiology of
leiomyomas. We propose to test our hypothesis in two specific aims. In Specific Aim 1 we will determine
the contribution of EFEMP1 to the tumorigenesis in leiomyoma. In Specific Aim 2 we will determine the
mechanism by which EFEMP1 is differentially expressed in leiomyoma versus myometrium. We predict that
the findings generated in this study will bring us one step closer to developing long-term nonhormonal
therapeutic and preventative interventions for these highly morbid tumors, underscoring the translational
potential of this study.
平滑肌瘤是一种高度弥漫性的子宫良性肿瘤,
50岁的女性。它们是美国子宫切除术的主要原因,占
在每年进行的60万例直肠切除术中,
成本尽管它们的流行和公共卫生的影响,细胞和分子机制调节,
平滑肌瘤的发展和生长还不清楚。表型上,这些肿瘤是不同的
从邻近的正常组织中分离出来,这主要是由于细胞外基质成分的过量产生。我们和
其他人已经证明,在LEIO和MYO之间差异表达的基因中,
EFEMP 1,表明在这些肿瘤的发病机制中的作用。在20个差异表达最大的基因中,
基因,我们确定了表皮生长因子含有纤维蛋白样细胞外基质1(EFEMP 1)。EFEMP1
编码一种纤蛋白(fibulin-3; FBLN 3),这是一个细胞外基质糖蛋白家族,
证实在血管生成、细胞外基质产生、器官形成和细胞增殖中发挥作用。
形态和生长。EFEMP 1的差异表达与肿瘤生长有关,
血管生成和细胞外基质的产生。具体来说,下调
已经证明EFEMP 1的表达促进前列腺,肺,
子宫内膜癌和结肠直肠癌。EFEMP 1及其蛋白的表达模式和作用均不清楚。
产品已在平滑肌瘤中进行了研究。我们的实验室已经生成了初步数据,
EFEMP 1在平滑肌瘤中显著下调。基于其作为肿瘤抑制剂在各种
我们假设EFEMP 1的异常表达有助于肿瘤的病理生理学,
平滑肌瘤我们建议在两个特定的目标来测试我们的假设。在具体目标1中,我们将确定
EFEMP 1在平滑肌瘤发生中的作用。在具体目标2中,我们将确定
EFEMP 1在平滑肌瘤和子宫肌层中差异表达的机制。我们预测
这项研究的发现将使我们更接近于开发长期非激素性的
治疗和预防性干预这些高度病态的肿瘤,强调翻译
这项研究的潜力。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Erica E Marsh其他文献
Uterine Fibroids.
子宫肌瘤。
- DOI:
10.1001/jama.2024.0447 - 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Erica E Marsh;G. Wegienka;David R Williams - 通讯作者:
David R Williams
Endometrial Thickness as Diagnostic Triage for Endometrial Cancer Among Black Individuals.
子宫内膜厚度作为黑人子宫内膜癌的诊断分诊。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:28.4
- 作者:
K. Doll;Mindy Pike;Julianna G. Alson;Patrice Williams;Erin Carey;Til Stürmer;Mollie E. Wood;Erica E Marsh;Ronit Katz;Whitney R. Robinson - 通讯作者:
Whitney R. Robinson
Erica E Marsh的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Erica E Marsh', 18)}}的其他基金
Community-Centered Interventions for Improved Vaccine Uptake for COVID (CIVIC)
以社区为中心的干预措施,以提高新冠病毒疫苗的接种率 (CIVIC)
- 批准号:
10397699 - 财政年份:2021
- 资助金额:
$ 0.83万 - 项目类别:
Community-Centered Interventions for Improved Vaccine Uptake for COVID (CIVIC)
以社区为中心的干预措施,以提高新冠病毒疫苗的接种率 (CIVIC)
- 批准号:
10341279 - 财政年份:2021
- 资助金额:
$ 0.83万 - 项目类别:
Community-Centered Interventions for Improved Vaccine Uptake for COVID (CIVIC)
以社区为中心的干预措施,以提高新冠病毒疫苗的接种率 (CIVIC)
- 批准号:
10554421 - 财政年份:2021
- 资助金额:
$ 0.83万 - 项目类别:
Study of Ovarian Aging and Reserve in Young Women (SOAR)
年轻女性卵巢衰老和储备的研究(SOAR)
- 批准号:
9160613 - 财政年份:2017
- 资助金额:
$ 0.83万 - 项目类别:
Study of Ovarian Aging and Reserve in Young Women (SOAR)
年轻女性卵巢衰老和储备的研究(SOAR)
- 批准号:
10359026 - 财政年份:2017
- 资助金额:
$ 0.83万 - 项目类别:
Study of Ovarian Aging and Reserve in Young Women (SOAR)
年轻女性卵巢衰老和储备的研究(SOAR)
- 批准号:
9859422 - 财政年份:2017
- 资助金额:
$ 0.83万 - 项目类别:
ELLAS Environment, Leiomyomas, Latinas and Adiposity Study
ELLAS 环境、平滑肌瘤、拉丁裔和肥胖研究
- 批准号:
9395499 - 财政年份:2016
- 资助金额:
$ 0.83万 - 项目类别:
Building Bridges, Breaking Barriers: An Academic-Community Partnership to Address Disparities in Uterine Fibroids
搭建桥梁,打破障碍:学术界合作解决子宫肌瘤的差异
- 批准号:
9113359 - 财政年份:2015
- 资助金额:
$ 0.83万 - 项目类别:
Role of MicroRNA-29 in Uterine Leiomyoma Pathogenesis
MicroRNA-29 在子宫平滑肌瘤发病机制中的作用
- 批准号:
8717698 - 财政年份:2013
- 资助金额:
$ 0.83万 - 项目类别:
Role of MicroRNA-29 in Uterine Leiomyoma Pathogenesis
MicroRNA-29 在子宫平滑肌瘤发病机制中的作用
- 批准号:
8571891 - 财政年份:2013
- 资助金额:
$ 0.83万 - 项目类别:
相似海外基金
Broadening Participation Research: Understanding faculty attitudes, competency, and perceptions of providing career advising to African American STEM students at HBCUs
扩大参与研究:了解教师对 HBCU 的非裔美国 STEM 学生提供职业建议的态度、能力和看法
- 批准号:
2306671 - 财政年份:2023
- 资助金额:
$ 0.83万 - 项目类别:
Continuing Grant
Cognitive Behavioral Faith-based Depression Intervention For African American Adults (CB-FAITH): An Effectiveness And Implementation Trial
非裔美国成年人基于认知行为信仰的抑郁干预 (CB-FAITH):有效性和实施试验
- 批准号:
10714464 - 财政年份:2023
- 资助金额:
$ 0.83万 - 项目类别:
DELINEATING THE ROLE OF THE HOMOCYSTEINE-FOLATE-THYMIDYLATE SYNTHASE AXIS AND URACIL ACCUMULATION IN AFRICAN AMERICAN PROSTATE TUMORS
描述同型半胱氨酸-叶酸-胸苷酸合成酶轴和尿嘧啶积累在非裔美国人前列腺肿瘤中的作用
- 批准号:
10723833 - 财政年份:2023
- 资助金额:
$ 0.83万 - 项目类别:
Preventing Firearm Suicide Deaths Among Black/African American Adults
防止黑人/非裔美国成年人因枪支自杀死亡
- 批准号:
10811498 - 财政年份:2023
- 资助金额:
$ 0.83万 - 项目类别:
Exploring PTSD Symptoms, Barriers and Facilitators to Mindfulness-based Stress Reduction for Justice-Involved Black/African American Female Adolescents and Parents/Caregivers
探索创伤后应激障碍 (PTSD) 症状、障碍和促进因素,为涉及正义的黑人/非裔美国女性青少年和父母/照顾者进行基于正念的减压
- 批准号:
10593806 - 财政年份:2023
- 资助金额:
$ 0.83万 - 项目类别:
BCSER - PVEST: A Dynamic Framework for Investigating STEM Interest, Attitude and Identity Among African American Middle School Students
BCSER - PVEST:调查非裔美国中学生 STEM 兴趣、态度和身份的动态框架
- 批准号:
2327055 - 财政年份:2023
- 资助金额:
$ 0.83万 - 项目类别:
Standard Grant
Making the Connection: Understanding the dynamic social connections impacting type 2 diabetes management among Black/African American men
建立联系:了解影响黑人/非裔美国男性 2 型糖尿病管理的动态社会联系
- 批准号:
10782674 - 财政年份:2023
- 资助金额:
$ 0.83万 - 项目类别:
Building a Community-Based Mental Health Literacy Intervention for African American Young Adults
为非裔美国年轻人建立基于社区的心理健康素养干预措施
- 批准号:
10738855 - 财政年份:2023
- 资助金额:
$ 0.83万 - 项目类别:
African American Literature in "post" Post-Racial America
“后”后种族美国中的非裔美国文学
- 批准号:
23K00376 - 财政年份:2023
- 资助金额:
$ 0.83万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Neurovascular Control of Renal Blood Flow During Exercise in African American Adults
非裔美国成年人运动期间肾血流的神经血管控制
- 批准号:
10653381 - 财政年份:2023
- 资助金额:
$ 0.83万 - 项目类别: