ESTROGEN RECEPTOR-BETA PROTEIN IN CANCER DIAGNOSIS

雌激素受体-β 蛋白在癌症诊断中的应用

• 批准号: 6298861
• 负责人: ROBERT J CHRISTY
• 金额: $ 10万
• 依托单位: GENETEX, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6298861
• 关键词: biomarker; breast neoplasms; estrogen receptors; human tissue; immunocytochemistry; laboratory mouse; molecular cloning; monoclonal antibody; neoplasm /cancer diagnosis; protein localization

DESCRIPTION: The cloning of the ER-Beta receptor has prompted investigators to reevaluate the molecular basis for estrogen action and the role of estrogen receptors in tumors from tissues where ER-Beta is normally expressed. We hypothesize that the alterations in the amounts and/or cellular localization of ER-Beta and its splice variant isoforms are clinically important biological feature in breast cancer and other tumors (e.g. ovary, prostate). To determine if ER-Beta will be a biomarker that can provide clinicians with new prognostic and predictive information we propose the following experiments. In Phase I of this project we will prepare the molecular reagents necessary for analysis of ER-Beta in breast and other cancers and determine the protein and mRNA expression levels in normal and tumor cell lines. We will then measure the expression levels of the ER-Beta isoforms in human breast tumor samples. In Phase II of this project we will optimize conditions of current and new monoclonal antibodies for immunohistochemistry, and we will continue tumor analysis by doing a large retrospective study of patients whom received no systemic adjuvant therapy following local surgery. This type of study provides an ideal setting for evaluation of the importance of ER-Beta as a potential prognostic factor in breast cancer. PROPOSED COMMERCIAL APPLICATION: The production of monoclonal antibodies against the Estrogen Receptor Beta isoforms will provide researchers and clinicians important reagents to determine the mechanisms of action for this newly discovered receptor and its importance as a predicitive indicator in cancer. The specific isoforms that do show clinical relevance will then be used to produce a diagnostic kit so pathologists can test for ER-beta expression along with standard test for other steriod receptors (e.g. ER-alpha and Progesterone).

描述：ER-Beta受体的克隆促使研究人员 重新评价雌激素作用的分子基础及雌激素的作用 正常表达ER-β的组织中的肿瘤受体。我们 假设在数量和/或细胞定位上的变化 ER-β及其剪接变异体在临床上具有重要的生物学意义 乳腺癌和其他肿瘤(如卵巢、前列腺)的特征。要确定 如果ER-β将成为一种生物标志物，可以为临床医生提供新的预后和 预测信息，我们提出了以下实验。在这个项目的第一阶段 我们将准备分析ER-Beta所需的分子试剂 在乳腺癌和其他癌症中的表达，并测定蛋白质和mRNA的表达 在正常和肿瘤细胞系中的水平。然后我们将测量该表达式 人乳腺肿瘤标本中ER-β亚型水平的研究在这个项目的第二阶段 我们将优化现有的和新的单抗的条件 对于免疫组织化学，我们将通过做一个大型的 未接受系统辅助治疗的患者的回顾性研究 在当地做了手术之后。这种类型的研究提供了一个理想的环境 ER-β作为乳腺癌潜在预后因子的重要性评价 癌症。 建议的商业应用： 针对雌激素受体Beta亚型的单抗的生产将 为研究人员和临床医生提供重要的试剂以确定其发病机制 这一新发现的受体的作用及其作为预测指标的重要性 癌症。确实显示出临床相关性的特定亚型将被用于 生产一种诊断试剂盒，以便病理学家可以测试ER-β表达以及 其他类固醇受体(如ER-α和黄体酮)的标准测试。

项目成果

Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts.

• 发表时间: 2003-09
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: M. Bockhorn;Y. Tsuzuki;Lei Xu;A. Frilling;C. Broelsch;D. Fukumura