Gene Regulation by TGF-beta and Androgen Crosstalk

TGF-β 和雄激素串扰的基因调控

• 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
• 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

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）：通过信号转导途径的串扰，信号积分导致对不同环境输入的协调细胞反应。前列腺上皮细胞的行为和前列腺癌的进展受雄激素和TGF-β的调节，雄激素和TGF-β激活了两个不同的信号通路，这些信号通路调节正常和恶性细胞功能，并且具有极大的生理和病理学重要性。雄激素受体和TGF-β激活的SMAD的物理和功能相互作用与雄激素和TGF-β信号的串扰有关。在这里，我建议确定在调节前列腺上皮细胞中基因表达中TGF-β和雄激素信号传导的机理。具体而言，我将确定由TGF-beta和雄激素差异地共同调节的转录靶标子集，并在具有差异转录响应的不同启动子处定义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中信号整合机制，并可能为前列腺癌治疗的机制指导的药物设计提供基础。