FUNCTIONAL ANALYSIS OF PTEN IN PROSTATE CANCER

PTEN 在前列腺癌中的功能分析

• 批准号: 6089850
• 负责人: YOUNG E WHANG
• 金额: $ 13.01万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-16 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6089850
• 关键词: Adenoviridae; SCID mouse; androgens; apoptosis; disease /disorder model; enzyme activity; gene therapy; hormone regulation /control mechanism; membrane proteins; mutant; neoplasm /cancer chemotherapy; nonhuman therapy evaluation; phosphatidylinositol 3 kinase; phosphomonoesterases; prostate neoplasms; protein localization; site directed mutagenesis; tumor suppressor proteins

DESCRIPTION (Applicant's Description): Research Plan: The main goal of this proposal is to define how the PTEN phosphatase acts to suppress tumor formation and to exploit this knowledge to design novel therapeutic approaches to prostate cancer. Our preliminary studies have established that PTEN expression is frequently lost in prostate cancer at the transcriptional level and that PTEN loss in tumor cells leads to excess cell survival signaling. In Aim 1, we will test the role of membrane localization on PTEN function by determining the effect of membrane targeted mutants of PTEN. In Aim 2, we will investigate the role of PTEN in mediating sensitivity to apoptosis induced by detachment from matrix, known as anoikis. We will characterize the effect of PTEN in sensitizing prostate tumor cells to anoikis and investigate the mechanisms of anoikis induction. In Aim 3, we will characterize the effect of PTEN expression in sensitizing cancer cells to a p optotic stimuli in vitro and investigate the effect of PTEN on tumorigenicity and sensitivity to chemotherapy and androgen deprivation in vivo in a prostate cancer xenograft animal model. This project will test the hypothesis that reconstitution of PTEN expression will reverse resistance to m u ltiple apoptotic stimuli associated with prostate cancer cells and represents a novel strategy for enhancing the efficacy of prostate cancer treatment.

描述（申请人的描述）： 研究计划：该提案的主要目标是定义 PTEN 如何 磷酸酶起到抑制肿瘤形成的作用，并利用这一知识来 设计前列腺癌的新治疗方法。 我们的初步 研究已证实 PTEN 表达在前列腺中经常丢失 转录水平上的癌症，肿瘤细胞中 PTEN 缺失导致 过量的细胞生存信号。在目标1中，我们将测试膜的作用 通过确定膜靶向的作用来定位 PTEN 功能 PTEN 突变体。在目标 2 中，我们将研究 PTEN 在介导中的作用 对由基质脱离引起的细胞凋亡（称为失巢凋亡）的敏感性。 我们将描述 PTEN 在使前列腺肿瘤细胞对 失巢凋亡并研究失巢凋亡诱导机制。在目标 3 中，我们将 表征 PTEN 表达对癌细胞敏感的影响 体外 p 光刺激并研究 PTEN 对 致瘤性以及对化疗和雄激素剥夺的敏感性 前列腺癌异种移植动物模型中的体内。该项目将测试 假设重建 PTEN 表达将逆转耐药性 与前列腺癌细胞相关的多种凋亡刺激 代表了一种增强前列腺癌疗效的新策略 治疗。