There are data to suggest that gain of function of Lrp5 or-6 is important to breast cancer. Some human breast cancer cells have an autocrine Wnt signaling loop. Recently, a splice variant of Lrp5, DLrp5, was found in the majority of breast tumors,Bortezomib and was required for their continued growth. The deletion of the variant exons by splicing was associated with resistance to inhibition by Dkk1. These data suggest that ectopic Wnt signaling could be an important source of growth dysregulation in breast tumors. These tumors are not all basaloid, they include tumors of many classes, which suggests that the Lrp5-dependent growth pathway could become viable in many candidate tumor precursor cell types. Lrp5 and-6 are co-expressed in the majority of basal cells. Lrp6 co-expression is high enough that the absence of Lrp5 has no effect on Wnt transactivation in response to Wnt3A. However, there is a very specific effect of the loss of Lrp5 on the maintenance of adult somatic stem cell activity. This corresponds to the lack of tumorigenicity of Wnt1 in Lrp52/2 mammary glands. This could be explained by the BYL719 following scenarios-1) Lrp5 has a distinct function in mammary stem cell biology compared to Lrp6, 2) Lrp5 expression augments Lrp6 expression to push the total expression over a critical threshold for growth promotion, 3) both Lrp5 and-6 are required for the stem cell function, 4) the ligand for Lrp5/Fzd is not Wnt1/Wnt3A, or 4) Lrp5 has a different subcellular presentation from Lrp6. Often, Lrp5/6 are used in experiments interchangeably, since they exhibit high sequence homology. Though they show similar expression patterns in embryonic and adult tissues, they have distinct functions. For example, an allelic series of mutations in Lrp5 and 6 in mouse embryos revealed that the Lrp5 loss in combination with Lrp6 loss produces a more severe phenotype than Lrp6 loss alone, and that Lrp6 loss is more severe than Lrp5 loss alone. The loss of Lrp5 tends to produce a subset of the phenotypes typical of Lrp6 null mice.