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Role of Ets Genes in transformation and Differentiation

Ets 基因在转化和分化中的作用

基本信息

批准号：
7618842
负责人：
Dennis K Watson
金额：
$ 116.37万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-30 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7618842
关键词：
Role Ets Genes transformation Differentiation

项目摘要

DESCRIPTION (provided by applicant): Although it is established that the Ets family of transcription factors control specific genes that contribute to normal and aberrant processes, identification of their roles in tumor metastasis remains an unresolved area requiring further investigation. Ets factors can be positive or negative regulators, and they can be intrinsic to the malignant cells or can affect stromal cells that indirectly influence cell movement. The members of this Program Project Grant will use in vitro and in vivo approaches to elucidate the upstream and downstream pathways that mediate Ets function, both in normal development and in cancer. The Program consists of three interactive Projects supported by three cores. Project 1 will test the hypothesis that the Ets factor PDEF controls multiple aspects of the multi-step metastatic process and therefore, loss of PDEF expression is a key event in the development of invasive breast cancer. Project 2 will examine a novel pathway in tumor cells that results in over-accumulation of a metastasis-inducing signaling receptor, FGF receptor; and analyze how Ets1 mediates this aberrant signaling event in promoting cell motility. Project 3 will further assess the mechanisms whereby Fli1 and Ets1 function as critical regulators of stromal homeostasis in healthy tissues, as well as their contribution to formation of reactive stroma in cancer. Specifically, Project 3 will test the hypothesis that Ets factors are integrators of the TGF-b/CTGF and Ras-MAPK signaling pathways in regulation of ECM remodeling. This in turn affects cell migration, cell survival and recruitment of perivascular cells to the newly formed vessels. Thus, the Program Project proposes experiments to elucidate the molecular pathways that underlie the roles of Ets factors in cell migration, invasion and metastasis and angiogenesis. The long-term goal of this Program is to gain new insights that will provide novel approaches for improved diagnosis and treatment of cancer.

描述(申请人提供)：尽管已确定ETS转录因子家族控制特定的基因，这些基因有助于正常和异常的过程，但确定它们在肿瘤转移中的作用仍然是一个有待进一步研究的领域。ETS因子可以是积极的或消极的调节因素，它们可以是恶性细胞的内在因素，也可以影响间质细胞，从而间接影响细胞的运动。该计划项目赠款的成员将使用体外和体内方法来阐明在正常发育和癌症中介导ETS功能的上游和下游途径。该方案由三个核心支持的三个互动项目组成。项目1将验证这一假设，即ETS因子PDEF控制多步骤转移过程的多个方面，因此，PDEF表达的丢失是浸润性乳腺癌发展中的关键事件。项目2将研究肿瘤细胞中一种导致转移诱导信号受体--成纤维细胞生长因子受体过度积累的新途径；并分析Ets1如何介导这一异常信号事件促进细胞运动。项目3将进一步评估FLI1和Ets1在健康组织中作为基质稳态的关键调节因子的作用机制，以及它们对癌症中反应性基质形成的贡献。具体地说，项目3将检验ETS因子是调节ECM重塑的TGF-b/CTGF和Ras-MAPK信号通路的整合因子的假设。这反过来影响细胞迁移、细胞存活和血管周围细胞对新形成的血管的募集。因此，该计划计划建议进行实验，以阐明ETS因子在细胞迁移、侵袭和转移以及血管生成中所起作用的分子途径。该计划的长期目标是获得新的见解，为改进癌症的诊断和治疗提供新的方法。

项目成果

期刊论文数量（47）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Understanding the role of ETS-mediated gene regulation in complex biological processes.

DOI：
10.1016/b978-0-12-407190-2.00001-0
发表时间：
2013
期刊：
ADVANCES IN CANCER RESEARCH
影响因子：
0
作者：
Findlay, Victoria J.;LaRue, Amanda C.;Turner, David P.;Watson, Patricia M.;Watson, Dennis K.
通讯作者：
Watson, Dennis K.

Prostate-Derived ETS Factor Regulates Epithelial-to-Mesenchymal Transition through Both SLUG-Dependent and Independent Mechanisms.