ERBB1 AND ERBB2 IN TUMOR MOTILITY AND METASTASIS

ERBB1 和 ERBB2 在肿瘤运动和转移中的作用

• 批准号: 6628144
• 负责人: JEFFREY E SEGALL
• 金额: $ 30.06万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-15 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6628144
• 关键词: G protein; adenocarcinoma; athymic mouse; breast neoplasms; cell motility; chemotaxis; epidermal growth factor; female; growth factor receptors; guanine nucleotide binding protein; intravital microscopy; laboratory rat; metastasis

DESCRIPTION: (Adapted from the investigator's abstract) The proteins ErbB1 and ErbB2 have been found to be important indicators of poor prognosis in breast cancer. However, the mechanisms by which these molecules contribute to metastasis have not been established. In particular, determination of whether there is a rate limiting step for metastasis which is determined by these molecules is unknown. Identification of the stage of metastasis that is enhanced by ErbB1 and ErbB2 together with the molecular mechanism is critical for determining approaches for treatment and prognosis of breast cancer. He has developed new methods for evaluating tumor cells in the primary tumor, blood and target organs, and will use these methods for evaluating tumor cells in the primary tumor, blood and target organs, and will use these methods to provide important information regarding how ErbB1 and ErbB2 function in metastasis. The objective of this proposal is to determine whether chemotaxis stimulated by ErbB1 and ErbB2 is rate-limiting for metastasis. The first specific aim will be to complete development of a metastasis assay that will provide information of blood burden, cell arrest in the lungs and metastasis formation in the lungs. A pair of well-characterized rat mammary adenocarcinoma cell lines using orthotopic implantation in a syngeneic host are being used to develop the assay. The assay will then be applied to human mammary adenocarcinoma cell lines implanted in nude mice. The second specific aim will be to use this assay to evaluate the contributions of ErbB1 and ErbB2 to metastasis in terms of chemotaxis and mitogenesis. The third specific aim will evaluate the roles of the rho family of small G proteins in metastasis.

描述：（改编自研究者的摘要）蛋白质 ErbB1 和 ErbB2被发现是乳腺预后不良的重要指标 癌症。然而，这些分子促成的机制 转移尚未确定。特别是，确定是否 转移有一个限速步骤，这是由这些决定的 分子未知。转移阶段的识别 ErbB1和ErbB2共同增强的分子机制至关重要 用于确定乳腺癌的治疗和预后方法。他有 开发了评估原发肿瘤、血液中肿瘤细胞的新方法 和靶器官，并将使用这些方法来评估肿瘤细胞 原发肿瘤、血液和靶器官，并将使用这些方法提供 有关 ErbB1 和 ErbB2 在转移中如何发挥作用的重要信息。这 该提案的目的是确定趋化性是否由 ErbB1 和 ErbB2 是转移的限速剂。第一个具体目标是 完成转移测定的开发，该测定将提供以下信息： 血液负荷、肺部细胞停滞和肺部转移形成。一个 使用一对充分表征的大鼠乳腺癌细胞系 同基因宿主中的原位植入正在被用来开发 化验。该测定随后将应用于人类乳腺癌细胞 线植入裸鼠体内。第二个具体目标是使用这种测定法 评估 ErbB1 和 ErbB2 对转移的贡献 趋化性和有丝分裂。第三个具体目标将评估 转移中小 G 蛋白的 rho 家族。