Wnt signaling in mammary development and cancer

描述：（由申请人提供）分泌蛋白的Wnt家族发挥作用， 在发育中的各种关键作用及其细胞内信号传导 在许多人类癌症中激活。几种Wnt蛋白与 在乳腺发育的调节中，异常的Wnt信号传导可以 导致小鼠乳腺肿瘤。Wnt蛋白被认为是通过细胞表面 由卷曲蛋白家族的蛋白质和LRP 5或LRP 6组成的受体。 然而，单个受体成分的功能和特异性 Wnt配体-受体相互作用的机制尚不清楚。这项研究的目的是 将研究单个Wnt蛋白的功能及其 受体在乳腺发育和肿瘤发生中的作用 细胞培养物和小鼠组合中的活化和信号拮抗作用 模型系统LRP 6在乳腺发育和Wnt信号转导中的作用将 与Wnt-Frizzled和Wnt-LRP的特异性一起探索 交互.将测试体内拮抗Wnt信号传导的方法。 它们对小鼠乳腺发育和预防癌前病变的影响 将被确定。激活致癌Wnt的作用 乳腺中的信号传导将使用可诱导的表达来测试， 系统，并使用DNA阵列分析基因表达的变化。 这些实验将阐明Wnt蛋白的作用机制和功能， 乳腺肿瘤。由于异常的Wnt表达和信号传导是 与人类乳腺癌相关，结果可能适用于未来 Wnt受体调节作为治疗干预手段的策略。

DESCRIPTION: (provided by applicant) The Wnt family of secreted proteins plays a variety of crucial roles in development and their intracellular signaling pathway is activated in many human cancers. Several Wnt proteins are implicated in the regulation of mammary gland development, and aberrant Wnt signaling can cause mammary tumors in mice. Wnt proteins are thought to act via cell surface receptors composed of proteins of the Frizzled family and either LRP5 or LRP6. However, the functions of individual receptor components, and the specificity of Wnt ligand-receptor interactions, remain unclear. The goals of this research will be to investigate the functions of individual Wnt proteins and their receptors in mammary development and tumorigenesis by studying signal activation and signal antagonism in a combination of cell culture and mouse model systems. The roles of LRP6 in mammary development and Wnt signaling will be explored, together with the specificity of Wnt-Frizzled and Wnt-LRP interactions. Methods of antagonizing Wnt signaling in vivo will be tested. Their effects on mouse mammary development, and on preventing premalignant hyperplasia, will be determined. The effects of activating oncogenic Wnt signaling in the mammary gland will be tested using an inducible expression system and the resulting changes in gene expression analyzed using DNA arrays. These experiments will elucidate mechanisms and functions of Wnt proteins in neoplasia of the mammary gland. Since aberrant Wnt expression and signaling is associated with human breast cancer, the results may be applicable to future strategies of Wnt receptor modulation as a means of therapeutic intervention.