乳腺的发育和病变受系统性的激素信号及局部的生长因子信号严密的调控。在基金委青年科学基金项目的资助下，我们前期的研究首次发现了Rspo1是一个新的激素响应因子，它与Wnt4协同作用促进乳腺干细胞的自我更新。然而，产生Rspo1的细胞不表达激素受体，激素必须要通过一个未知的旁分泌因子的介导才能调控Rspo1的表达。在初期的探索中，我们还发现Rspo1在乳腺中有新的细胞靶点，Rspo1够通过正反馈机制作用于激素受体阳性的细胞，促进雌激素受体ERa的表达。本项目的申请致力于发现调控Rspo1表达的旁分泌因子，阐明激素调控Rspo1表达的分子机制，探索Rspo1影响激素受体表达的新功能，揭示激素信号与Rspo1的正反馈相互作用。本项目的完成将有助于阐明激素与生长因子相互作用的信号网络，全面了解Rspo1在乳腺发育中的功能和作用机理，为乳腺癌的预防和治疗提供理论基础和新思路。

Concerted action of systemic hormones and local growth factors are pivotal to mammary development and tumorigenesis. Our recent work supported by NSFC revealed that R-spondin1 (Rspo1) is a novel mediator of hormonal signals, estrogen and progesterone. Rspo1 cooperates with Wnt4 to promote mammary stem cell self-renewal. However, Rspo1 is expressed in hormone receptor-negative luminal cells, the mechanism through which hormones regulate Rspo1 must be indirect and the mediator remains elusive. Furthermore, our preliminary data suggest that Rspo1 can target hormone receptor-positive cells and upregulate their ERa expression. This proposal aims to investigate the molecular mechanisms through which Rspo1 is regulated by hormones, explore novel roles of Rspo1 in mammary development and uncover the potential positive feedback between hormonal signaling and Rspo1.This study will enable better understanding of the underlying molecular mechanism through which Rspo1 regulates mammary development. This research will improve our understanding on the hormonal regulation mechanisms on mammary development, holding promise for developing novel strategy for breast cancer treatment.