Gene Regulation by TGF-beta and Androgen Crosstalk

TGF-β 和雄激素串扰的基因调控

基本信息

批准号：
6999061
负责人：
YURIY SHOSTAK
金额：
$ 4.14万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2006-05-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6999061
关键词：
androgen receptor androgens biological signal transduction carcinoma cell transformation epithelium gene expression genetic promoter element genetic regulation genetic transcription hormone regulation /control mechanism hormone related neoplasm /cancer postdoctoral investigator prostate neoplasms protein protein interaction protein structure function tissue /cell culture transforming growth factors

项目摘要

DESCRIPTION (provided by applicant): Coordinated cellular responses to diverse environmental inputs result from signal integration through crosstalk of signal transduction pathways. The behavior of prostate epithelial cells and progression of prostate carcinoma are regulated by androgens and TGF-beta, which activate two distinct signaling pathways that regulate normal and malignant cell functions and are of great physiological and pathological importance. Physical and functional interactions of the androgen receptor and TGF-beta-activated Smads have been implicated in the crosstalk of androgen and TGF-beta signaling. Here, I propose to determine the mechanisms of TGF-beta and androgen signaling crosstalk in regulating gene expression in prostate epithelial cells. Specifically, I will identify subsets of transcriptional targets that are differentially co-regulated by TGF-beta and androgens and define molecular mechanisms of signaling crosstalk at distinct promoters with differential transcriptional responses. This study will contribute to our understanding of mechanisms of signal integration in normal and malignant cell physiology and may provide a basis for mechanism-directed drug design for prostate cancer therapy.

描述（由申请人提供）：细胞对不同环境输入的协调反应是通过信号转导途径的串扰进行信号整合的结果。前列腺上皮细胞的行为和前列腺癌的进展受到雄激素和TGF-β的调节，它们激活调节正常和恶性细胞功能的两种不同的信号通路，具有重要的生理和病理意义。雄激素受体和 TGF-β 激活的 Smad 之间的物理和功能相互作用与雄激素和 TGF-β 信号传导的串扰有关。在这里，我建议确定 TGF-β 和雄激素信号串扰调节前列腺上皮细胞基因表达的机制。具体来说，我将确定由 TGF-β 和雄激素差异共同调节的转录靶标子集，并定义具有差异转录反应的不同启动子处信号串扰的分子机制。这项研究将有助于我们理解正常和恶性细胞生理学中信号整合的机制，并可能为前列腺癌治疗的机制导向药物设计提供基础。