Mechanism of Wnt4 Signaling in the Breast.

摘要

Wnt proteins are a family of 19 secreted glycoproteins that regulate numerous aspects of mammalian development. The functions of one member of this family, Wnt4, include roles in ductal branching of the mammary gland. Its role is the breast is of significant importance because it mediates hormone signals during pregnancy and its overexpression leads to hyperplasia and premature alveolar differentiation. Previous studies have identified key components of the Wnt signaling pathway including Frizzled proteins and LDL receptor-related proteins (LRPs) as receptors for this pathway. Although these receptors have been identified, the specificity of Frizzled and LRPs for Wnt proteins is unclear and receptors involved in Wnt4 signaling in the breast are not known. Identifying the Wnt4 receptor will be crucial to understanding the mechanism by which overexpression of Wnts leads to hyperplasia and tumorigenesis. We have currently analyzed Frizzled and LRP expression at different stages of mammary development and in cell lines that respond/do not respond to Wnt4. We transiently transfected all receptors into Wnt4 non-responder cells and found two candidate Wnt4 receptors. These candidates were stably expressed in non- responder cells and shown to activate signaling in the presence of Wnt4.