Role of Cten in Prostate Cancer

Cten 在前列腺癌中的作用

• 批准号: 6879130
• 负责人: SU HAO LO
• 金额: $ 22.71万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6879130
• 关键词: actin binding protein; adhesions; cell adhesion molecules; cell migration; clinical research; disease /disorder model; gene expression; genetically modified animals; human tissue; laboratory mouse; neoplasm /cancer genetics; neoplastic cell; neoplastic process; pathologic process; prostate neoplasms; protein localization; protooncogene; tumor suppressor genes

DESCRIPTION (provided by applicant): Prostate cancer is the most common malignancy in North American men. However, the genetic events associated with the malignant transformation of prostatic cells are largely unknown. Identification of new prostate specific genes could provide new markers and could be instrumental for development of new treatment modalities. Tensin is a focal adhesion molecule that interacts with the actin cytoskeleton and mediates signal transduction. During the course of isolating tensin family genes, we have identified a novel C-terminal tensin-like molecule, cten. Cten is a 715 amino acid molecule containing src homology 2 and phosphotyrosine-binding domains that are similar to tensins. However, cten does not have the actin-binding activities found in tensin family and is much smaller in molecular mass. Interestingly, the expression of cten is restricted to prostate and placenta, and is often reduced/lost in prostate cancer/cell lines. In addition, human cten gene is located on chromosome 17q21, a region often deleted in prostate cancer. Cten localizes to focal adhesions, but unlike tensins, it is also found in nucleus. We hypothesize that cten is a prostate-specific tumor suppressor that plays an important role in signaling between focal adhesions and the nucleus; and that alteration of cten expression or function disrupts its normal actions and increases the risk for prostate cancer. The overall goal of this proposal is to determine whether the expression of cten can be used in early detection, diagnosis and monitoring of disease progression, and to study the function of cten in prostate cancer. There are three specific aims: Aim 1. To establish the value of cten expression patterns in prostate cancer diagnosis and prognosis. Aim 2. To determine the role of cten on the phenotype of prostate cancer cells, and elucidate the functions of its subcellular localization, using in vitro model systems. Aim 3. To determine the function of cten in prostate physiology and carcinogenesis, using in vivo models of transgenic mice expressing wild-type or mutated human cten.

描述（由申请人提供）：前列腺癌是北美男性最常见的恶性肿瘤。然而，与前列腺细胞恶性转化相关的遗传事件在很大程度上尚不清楚。新的前列腺特异性基因的鉴定可以提供新的标记，并且有助于开发新的治疗方式。张力蛋白是一种粘附斑分子，与肌动蛋白细胞骨架相互作用并介导信号转导。在分离张力蛋白家族基因的过程中，我们鉴定了一种新的C端张力蛋白样分子，cten。 Cten 是一个 715 个氨基酸的分子，含有 src 同源 2 和类似于张力蛋白的磷酸酪氨酸结合域。然而，cten 不具有张力蛋白家族中的肌动蛋白结合活性，并且分子量小得多。有趣的是，cten 的表达仅限于前列腺和胎盘，并且在前列腺癌/细胞系中经常减少/丢失。此外，人类cten基因位于染色体17q21上，该区域在前列腺癌中经常被删除。 Cten 定位于粘着斑，但与张力蛋白不同，它也存在于细胞核中。我们假设 cten 是一种前列腺特异性肿瘤抑制因子，在粘着斑和细胞核之间的信号传导中发挥重要作用； cten 表达或功能的改变会破坏其正常作用并增加患前列腺癌的风险。该提案的总体目标是确定cten的表达是否可以用于疾病进展的早期检测、诊断和监测，并研究cten在前列腺癌中的功能。 具体目标有以下三个： 目的 1. 建立 cten 表达模式在前列腺癌诊断和预后中的价值。 目标 2. 利用体外模型系统确定 cten 对前列腺癌细胞表型的作用，并阐明其亚细胞定位的功能。 目标 3. 使用表达野生型或突变的人 cten 的转基因小鼠体内模型确定 cten 在前列腺生理学和癌发生中的功能。