Wnt signaling in mammary development and cancer

描述：(申请人提供)WNT家族分泌蛋白发挥作用 发育过程中的多种关键作用及其细胞内信号转导 通路在许多人类癌症中被激活。与几个Wnt蛋白有关 在乳腺发育的调节中，Wnt信号的异常可以 导致小鼠乳腺肿瘤。WNT蛋白被认为通过细胞表面发挥作用 由Frizzled家族的蛋白质和LRP5或LRP6组成的受体。 然而，单个受体组分的功能和特异性 Wnt配体-受体之间的相互作用尚不清楚。这项研究的目标是 将研究单个Wnt蛋白的功能和它们的 通过研究信号研究乳腺发育和肿瘤发生中的受体 细胞培养与小鼠结合中的激活和信号拮抗 模型系统。LRP6在乳腺发育和Wnt信号转导中的作用 以及Wnt-FrizzledLRP和Wnt-LRP的特异性 互动。将测试体内拮抗Wnt信号的方法。 它们对小鼠乳腺发育和预防癌前病变的影响 增生症，将被确定。激活致癌Wnt的作用 乳腺中的信号将使用可诱导的表达进行测试 系统以及由此产生的基因表达的变化，使用DNA阵列进行分析。 这些实验将阐明Wnt蛋白的机制和功能。 乳腺肿瘤乳腺肿块。由于异常Wnt表达和信号转导 与人类乳腺癌相关的研究结果可能适用于未来 Wnt受体调控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.