Understanding Hormone Receptor and Oncogene Crosstalk

了解激素受体和癌基因串扰

• 批准号: 7116826
• 负责人: Jennifer C King
• 金额: $ 4.53万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-06-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7116826
• 关键词: Androgen Receptor; Breast; Cultured Cells; Development; Growth; Hormone Receptor; In Vitro; Malignant neoplasm of prostate; Molecular Target; Oncogenes; Oncogenic; Ovary; Pathway interactions; Prostate; Receptor Signaling; Research Proposals; Signal Pathway; Signal Transduction; Tumor Biology; c-myc Genes; cell growth; in vivo; insight; mouse model; research study; tumorigenic

DESCRIPTION (provided by applicant): Hormone receptor signaling is critical for normal and tumorigenic growth in ovary, breast, and prostate. Recent studies from our lab and others have shown that known oncogenes, such as c-myc and ErbB2, are involved in androgen receptor signaling in prostate cancer. However, the connectivity between the specific pathways is still poorly defined. The experiments in this research proposal will provide important insight into these interactions through the combined study of conditional mouse models and in vitro cell culture. Specifically, they will determine whether downstream oncogenic effectors can compensate for androgenic signaling in vivo, answer if the androgen receptor itself can act as an oncogene, and elucidate how the androgen receptor regulates its downstream targets to control cellular growth. A clear understanding of the crosstalk between hormone receptors and oncogenic signaling pathways is essential for tumor biology as well as the development of targeted molecular therapies.

描述（由申请人提供）：激素受体信号传导对于卵巢，乳房和前列腺的正常和致瘤生长至关重要。我们实验室和其他人的最新研究表明，在前列腺癌中，已知的癌基因（例如C-MYC和ERBB2）参与了雄激素受体信号传导。但是，特定途径之间的连通性仍然很差。该研究建议中的实验将通过对条件小鼠模型和体外细胞培养的联合研究为这些相互作用提供重要的见解。具体而言，他们将确定下游的致癌效应子是否可以补偿体内的雄激素信号传导，回答雄激素受体本身是否可以充当癌基因，并阐明雄激素受体如何调节其下游靶标以控制细胞生长。对激素受体和致癌信号通路之间的串扰的清晰了解对于肿瘤生物学以及靶向分子疗法的发展至关重要。

项目成果

Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesis.

• DOI: 10.1038/ng.371
• 发表时间: 2009-05
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: King, Jennifer C.;Xu, Jin;Wongvipat, John;Hieronymus, Haley;Carver, Brett S.;Leung, David H.;Taylor, Barry S.;Sander, Chris;Cardiff, Robert D.;Couto, Suzana S.;Gerald, William L.;Sawyers, Charles L.
• 通讯作者: Sawyers, Charles L.