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性截短的 由原癌基因c-erbBI编码的受体形式。（1-2） 来自PI实验室和其他机构的初步数据表明， 相关的原癌基因c-erbB 2和c-erbB 3也编码可溶性的 受体形式。(3-6)原癌基因c-erbB家族已经被 与乳腺癌和卵巢癌的发生有关。 在 在这项应用中，我们假设可溶性形式的受体编码 c-erbB家族的原癌基因可能在卵巢癌中起重要作用。 致癌作用和MAV作为疾病标志物具有临床实用性 活性，作为预后指标，和/或作为 未来的治疗方法。 为了验证这一假设，我们建议 在一个大的， 晚期卵巢癌患者队列研究。 我们将比较 血清可溶性受体表达与肿瘤c-erbB表达 通过免疫组织化学分析确定细胞。 然后我们将 比较c-erbB表达模式（血清和肿瘤样本）与 建立组织学和临床参数。 我们亦建议 阐明了可溶性c-erbB合成的分子基础 受体形式的卵巢肿瘤，并将测试这些能力， 可溶性受体在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.