TRUNCATED C-ERBB RECEPTORS IN WOMEN WITH OVARIAN CANCER

卵巢癌女性中 C-ERBB 受体截短

• 批准号: 3201879
• 负责人: NITA J MAIHLE
• 金额: $ 18.96万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3201879
• 关键词: biomarker; enzyme linked immunosorbent assay; epithelioma; female; genetic library; growth inhibitors; human subject; immunoaffinity chromatography; immunocytochemistry; immunoprecipitation; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplasm /cancer therapy; nucleic acid sequence; ovary neoplasms; protooncogene; receptor expression; recombinant DNA; tissue /cell culture

The PI's laboratory has recently discovered a novel, soluble truncated form of the receptor encoded by the proto-oncogene c-erbBI.(1-2) Preliminary data from the PI's laboratory and others suggest that the related proto-oncogenes, c-erbB2 and c-erbB3, also encode soluble receptor forms. (3-6) The c-erbB family of proto-oncogenes has been implicated in the development of both breast and ovarian carcinomas. In this application, we hypothesize that soluble forms of receptors encoded by the c-erbB family of proto-oncogenes may be important in ovarian carcinogenesis and mav have clinical utility as markers of disease activity, as prognostic indicators, and/or as potential targets for future therapeutic approaches. To test this hypothesis we propose to measure the serum levels of soluble forms of c-erbB receptors in a large cohort of women with advanced ovarian cancer. We will compare the expression of soluble receptors in serum with c-erbB expression in tumor cells as determined by immunohistochemical analysis. We will then compare c-erbB patterns of expression (in sera and tumor samples) with established histologic and clinical parameters. We also propose to delineate the molecular basis for the synthesis of soluble c-erbB receptor forms in ovarian tumors, and will test the ability of these soluble receptors to inhibit ovarian carcinoma cell growth in vitro.

PI的实验室最近发现了一部小说，可溶性的截断 由原始癌基因C-Erbbi编码的受体的形式（1-2） PI实验室的初步数据，其他数据表明 相关的原始基因，C-ERBB2和C-ERBB3，也编码可溶性 受体形式。 （3-6）原始基因的C-ERBB家族已经 与乳腺癌和卵巢癌的发展有关。 在 该应用程序，我们假设被编码的可溶性形式 由c-erbb家族的原始基因家族在卵巢中可能很重要 致癌作用和MAV具有临床用途作为疾病的标志 活动，作为预后指标和/或作为潜在目标 未来的治疗方法。 为了检验这一假设，我们建议 测量大型C-ERBB受体的血清水平 患有晚期卵巢癌的女性队列。 我们将比较 在肿瘤中具有C-ERBB表达的血清中可溶性受体的表达 通过免疫组织化学分析确定的细胞。 然后我们会 比较C-ERBB表达模式（在血清和肿瘤样品中）与 建立的组织学和临床参数。 我们还建议 描述合成可溶性C-ERBB的分子基础 卵巢肿瘤中的受体形式，将测试这些受体的能力 可溶性受体可在体外抑制卵巢癌细胞生长。