ERBB1 AND ERBB2 IN TUMOR MOTILITY AND METASTASIS

描述：(改编自研究人员摘要)ErbB1和ErbB1蛋白 ERBB2已被发现是乳腺癌预后不良的重要指标 癌症。然而，这些分子参与的机制 转移尚未确定。特别是，确定是否 转移有一个速率限制步骤，这是由这些决定的 分子是未知的。确定转移的阶段，即 ErbB1和ErbB2的协同增强及其分子机制是关键 用于确定乳腺癌的治疗和预后的方法。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 原发肿瘤、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。这个 这项建议的目的是确定趋化作用是否被刺激 ErbB1和ErbB2对转移具有限速作用。第一个具体目标将是 为了完成转移分析的开发，它将提供 血液负荷、肺部细胞停滞和肺部转移形成。一个 一对特性良好的大鼠乳腺腺癌细胞系 在同基因宿主体内的原位植入正在被用于开发 化验。然后，该分析将应用于人乳腺腺癌细胞 将细胞系植入裸鼠体内。第二个具体目标将是使用这种分析方法 评价ErbB1和ErbB2在肿瘤转移中的作用 趋化和有丝分裂。第三个具体目标将评估 Rho家族小G蛋白在肿瘤转移中的作用

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.