MECHANISMS OF ACTION OF THE MAMMARY ONCOGENE WNT 1

描述：WNT-1是一种乳腺癌基因，可导致乳腺增生症和乳腺癌。 小鼠乳腺激活时的致瘤性及其原因 某些乳腺上皮细胞在培养过程中的转化。基因 正常情况下在胎儿大脑形态发生中起作用。WNT-1编码一个 分泌的蛋白质，作用于细胞间的信号传递。这样做的目的是 研究建议是研究WNT-1在心脏疾病中的作用机制。 乳腺细胞转化，使用最近发现的两个来源 可溶性Wnt-1蛋白。Wnt-1蛋白的活性形式和任何 相关因素将被表征，并用于早期调查 WNT-1在乳腺细胞中的分子反应，并鉴定和 Wnt受体的特性。Wnt信号对白蛋白的影响 和β-连环蛋白，以及其他哺乳动物同源物将被评估 果蝇中可能的Wnt-1信号通路的组成部分。 快速酪氨酸磷酸化的蛋白质对WNT-1的反应 将被描述为。放射性标记的WNT-1将用于演示 与细胞的特异性结合，并通过交联剂和 亲和力标记。

DESCRIPTION: Wnt-1 is a mammary oncogene which causes hyperplasia and tumorigenesis when activated in mouse mammary gland and causes transformation of certain mammary epithelial cells in culture. The gene normally functions in fetal brain morphogenesis. Wnt-1 encodes a secreted protein that acts in cell-cell signalling. The goal of this research proposal is to investigate the mechanism of action of Wnt-1 in mammary cell transformation, using two recently identified sources of soluble Wnt-1 proteins. The active form of Wnt-1 protein and any associated factors will be characterized, and used to investigate early molecular responses to Wnt-1 in mammary cells, and to identify and characterize Wnt receptors. The effects of Wnt signals on plakoglobin and beta-catenin will be evaluated, as well as other mammalian homologs of components of the putative Wnt-1 signaling pathway in Drosophila. Proteins that are rapidly tyrosine phosphorylated in response to Wnt-1 will be characterized. Radiolabeled Wnt-1 will be used to demonstrate specific binding to cells and to identify receptors by cross-linking and affinity labeling.