TRUNCATED C-ERBB RECEPTORS IN WOMEN WITH OVARIAN CANCER

PI的实验室最近发现了一种新的、可溶的截断 原癌基因c-erbBI编码的受体形式(1-2) 来自PI实验室和其他人的初步数据表明， 相关的原癌基因c-erbB2和c-erbB3也编码可溶性 受体形式。(3-6)原癌基因c-erbB家族 与乳腺癌和卵巢癌的发生有关。在……里面 在这个应用中，我们假设可溶性形式的受体编码 原癌基因c-erbB家族在卵巢中可能起重要作用 癌变和MAV作为疾病的标志物具有临床应用价值 活动，作为预测指标和/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 检测大鼠血清可溶性c-erbB受体水平 患有晚期卵巢癌的女性队列。我们将比较 血清可溶性受体的表达与c-erbB在肿瘤中的表达 免疫组织化学分析所确定的细胞。到时候我们会的 比较c-erbB表达模式(在血清和肿瘤样本中)与 确定了组织学和临床参数。我们还建议 可溶性c-erbB合成的分子基础 在卵巢肿瘤中形成受体，并将测试这些受体的能力 可溶性受体体外抑制卵巢癌细胞生长。

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.