LRIG Proteins in mammary gland development and carcinogenesis

描述(由申请人提供)：本项目重点是对富含亮氨酸的跨膜重复蛋白Lrig1的机制分析。最近，LRIG蛋白作为新的膜受体调节剂出现，与乳腺生物学和肿瘤发生相关，包括ErbB途径的成员。该提议的中心假设是Lrig1在致癌受体的转录后调控中起关键作用，并且Lrig1在乳腺癌中的扰动有助于受体的异常表达，影响肿瘤的启动和/或进展。在这项建议中，我们将把我们的努力集中在两个独立的目标上，这两个目标将扩大我们对Lrig1在乳腺生物学和肿瘤发生中的功能的了解。在目标1中，我们将利用Lrig1基因敲除小鼠来确定Lrig1在乳腺发育和癌基因驱动的肿瘤发展中的作用。在目标2中，我们将研究Lrig1在雌激素受体-a和ErbB2之间的串扰中的作用以及对内分泌抵抗的影响。

DESCRIPTION (provided by applicant): This project focuses on a mechanistic analysis of the transmembrane leucine-rich repeat protein Lrig1. Lrig proteins have recently emerged as novel modulators of membrane receptors with relevancy to mammary gland biology and tumorigenesis, including members of the ErbB pathway. The central hypothesis of this proposal is that Lrig1 plays a critical role in the post-transcriptional regulation of oncogenic receptors ad that perturbation of Lrig1 in breast cancer contributes to aberrant receptor expression, impacting tumor initiation and /or progression. In this proposal, we will focus our efforts on two independent aims which will expand our knowledge of the function of the Lrig1 in mammary gland biology and tumorigenesis. In Aim 1, we will exploit the Lrig1 knockout mice to define the role of Lrig1 in mammary gland development and oncogene-driven tumor development. In Aim 2, we will examine the role of Lrig1 in crosstalk between the estrogen receptor-a and ErbB2 with implications for endocrine resistance.