Role of N-cadherin in Urothelial Neoplastic Progression

N-钙粘蛋白在尿路上皮肿瘤进展中的作用

• 批准号: 6752043
• 负责人: IAN CHARLES SUMMERHAYES
• 金额: $ 18.36万
• 依托单位: LAHEY CLINIC
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-15 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6752043
• 关键词: athymic mouse; biological signal transduction; bladder neoplasm; cadherins; cell cell interaction; fibroblasts; fusion gene; molecular oncology; neoplasm /cancer transplantation; neoplastic process; tissue /cell culture; transfection; vascular endothelium

DESCRIPTION (Adapted from the Applicant's Abstract): The long-term objectives of this project are to understand the role and mechanism of action of N-cadherin in the invasive process related to bladder carcinomas. Preliminary work has identified decreased invasive potential associated with the down regulation of N-cadherin in bladder carcinoma cells. We hypothesize that N-cadherin is a positive mediation in this model. To identify the molecular domain(s) of N-cadherin responsible for eliciting the invasive phenotype we will create chimeras between E- and N-cadherinn genes assaying for in vitro invasive capacity in appropriate transfected cells. We propose that the juxtamembrane domain (JMD) of N-cadherin is critical in generating the invasive behavior and this will be tested directly using a construct where the JMD of N-cadherin is deleted. The P120 protein is associated with the JMD of cadherins and is likely an important regulator of cadherin function. Distinct p120 isoforms have been identified in bladder carcinoma cells expressing different cadherins where p120-1A is the predominant isoform found in invasive, N-cadherin expressing bladder cells. To investigate the importance of this association for invasion, we will isolate clones of p120 isoforms and introduce p120-1A into bladder cell lines expressing E- or E-/N-cadherin lacking p1201A. We further propose to identify the signaling pathway(s) linked to N-cadherin and invasion, initially evaluating established signaling events implicated in this process. Since the goals of this proposal focus upon the role of N-cadherin in invasion of bladder carcinoma cells, we propose to develop new in vitro models representing different states of the metastatic process in which we can investigate the role(s) of N-cadherin. Validation of N-cadherin in bladder tumor metastasis would identify it as a potential marker of invasion and a possible therapeutic target for the future.

描述（改编自申请人摘要）：长期目标

项目成果

Restoration of plakoglobin expression in bladder carcinoma cell lines suppresses cell migration and tumorigenic potential.

• DOI: 10.1038/sj.bjc.6602651
• 发表时间: 2005-06-20
• 期刊: BRITISH JOURNAL OF CANCER
• 影响因子: 8.8
• 作者: Rieger-Christ, KM;Ng, L;Hanley, RS;Durrani, O;Ma, H;Yee, AS;Libertino, JA;Summerhayes, IC
• 通讯作者: Summerhayes, IC

Epidermal growth factor receptor status and the response of bladder carcinoma cells to erlotinib.

表皮生长因子受体状态和膀胱癌细胞对厄洛替尼的反应。

• DOI: 10.1016/j.juro.2007.05.113
• 发表时间: 2007
• 期刊: The Journal of urology
• 作者: Jacobs,MicahA;Wotkowicz,Chad;Baumgart,EgbertD;Neto,BrasilSilva;Rieger-Christ,KimberlyM;Bernier,Trisha;Cohen,MichaelS;Libertino,JohnA;Summerhayes,IanC
• 通讯作者: Summerhayes,IanC