LRIG Proteins in mammary gland development and carcinogenesis

项目描述（由申请人提供）：本项目主要研究富亮氨酸跨膜重复蛋白Lrig1的机制分析。Lrig蛋白最近被发现是与乳腺生物学和肿瘤发生相关的膜受体的新型调节剂，包括ErbB途径的成员。该提案的中心假设是Lrig1在致癌受体的转录后调控中起关键作用，并且乳腺癌中Lrig1的扰动会导致受体表达异常，影响肿瘤的发生和/或进展。在这个提案中，我们将集中精力在两个独立的目标上，这将扩大我们对Lrig1在乳腺生物学和肿瘤发生中的功能的认识。在Aim 1中，我们将利用Lrig1敲除小鼠来确定Lrig1在乳腺发育和癌基因驱动肿瘤发展中的作用。在Aim 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及其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.