ESTROGEN RECEPTOR-BETA PROTEIN IN CANCER DIAGNOSIS

描述：ER-β受体的克隆促使研究人员 重新评估雌激素作用的分子基础和雌激素的作用 ER-β正常表达的组织中的肿瘤受体。我们 假设，在数量和/或细胞定位的变化， ER-β及其剪接变体亚型是临床上重要的生物学活性物质， 乳腺癌和其他肿瘤（如卵巢、前列腺）的特征。以确定 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， 预测信息，我们提出以下实验。在第一阶段， 我们将准备分析ER β所需的分子试剂 在乳腺癌和其他癌症中， 在正常和肿瘤细胞系中的水平。然后我们将测量 人乳腺肿瘤样品中ER-β亚型的水平。在第二阶段， 项目我们将优化当前和新的单克隆抗体的条件 进行免疫组织化学，我们将继续进行肿瘤分析， 未接受全身辅助治疗的患者的回顾性研究 局部手术后。这种类型的研究提供了一个理想的设置， 评价ER-β作为乳腺癌潜在预后因子的重要性 癌 拟定商业应用： 针对雌激素受体β亚型的单克隆抗体的生产将 为研究人员和临床医生提供重要的试剂，以确定 这种新发现的受体的作用及其作为预测指标的重要性， 癌 然后将显示临床相关性的特定亚型用于 生产诊断试剂盒，以便病理学家可以测试ER-β表达沿着 其他类固醇受体（如ER-α和孕酮）的标准测试。

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).