FUNCTIONAL ANALYSIS OF PTEN IN PROSTATE CANCER

PTEN 在前列腺癌中的功能分析

基本信息

批准号：
6863678
负责人：
YOUNG E WHANG
金额：
$ 6.51万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
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/6863678
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

项目摘要

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 磷酸酶的作用是抑制肿瘤形成并利用这种知识设计新颖的前列腺癌治疗方法。我们的初步研究已经确定，PTEN表达在前列腺中经常丢失转录水平的癌症，肿瘤细胞中的PTEN丧失导致过多的细胞存活信号传导。在AIM 1中，我们将测试膜的作用通过确定靶向膜的影响，对PTEN功能的定位 PTEN的突变体。在AIM 2中，我们将研究PTEN在中介中的作用对基质（称为Anoikis）脱离引起的凋亡的敏感性。我们将表征PTEN在将前列腺肿瘤细胞敏化中的影响 Anoikis并研究Anoikis诱导的机制。在AIM 3中，我们将表征了PTEN表达在使癌细胞敏化中的影响 P Optotic刺激体外并研究PTEN对PTEN的影响对化疗和雄激素剥夺的肿瘤性和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PTEN表达的重构将逆转抵抗与前列腺癌细胞和代表了增强前列腺癌功效的新型策略治疗。