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: 6697531
• 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/6697531
• 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：（改编自研究者摘要）蛋白质ErbB1和 ErbB2是乳腺癌预后不良的重要指标 癌然而，这些分子有助于 尚未确定转移。特别是，确定是否 存在转移的速率限制步骤，其由这些决定 分子未知。确定转移的阶段，即 ErbB1和ErbB2的增强作用及其分子机制是关键 用于确定乳腺癌的治疗和预后方法。他 开发了新的方法来评估原发肿瘤，血液中的肿瘤细胞， 和靶器官，并将使用这些方法来评估肿瘤细胞在 原发性肿瘤，血液和靶器官，并将使用这些方法提供 关于ErbB1和ErbB2如何在转移中发挥作用的重要信息。的 该建议的目的是确定是否有趋化刺激 ErbB1和ErbB2是转移的限速因子。第一个具体目标是 以完成转移测定的开发， 血液负荷、肺中的细胞停滞和肺中的转移形成。一 一对充分表征的大鼠乳腺癌细胞系， 在同基因宿主中的原位植入被用于开发 比色法然后将该试验应用于人乳腺癌细胞 移植到裸鼠体内。第二个具体目标将是使用该测定法 评价ErbB1和ErbB2在肿瘤转移中的作用， 趋化性和有丝分裂。第三个具体目标将评估以下方面的作用： rho家族小G蛋白在转移中的作用