TI - The Internally Truncated LRP5 Receptor Presents a Therapeutic Target in Breast Cancer LRP5Delta in Breast Cancer . AB - Background Breast cancer is a common malignant disease , which may be caused by a number of genes deregulated by genomic or epigenomic events . Deregulated WNT/beta-catenin signaling with accumulation of beta-catenin is common in breast tumors , but mutations in WNT signaling pathway components have been rare . An aberrantly spliced internally truncated LRP5 receptor ( LRP5Delta666-809 , LRP5Delta ) was shown recently to be resistant to DKK1 inhibition , and was required for beta-catenin accumulation in hyperparathyroid tumors and parathyroid tumor growth . Methodology/Principal Findings Here we show , by reverse transcription PCR and Western blot analysis , that LRP5Delta is frequently expressed in breast tumors of different cancer stage ( 58-100% ) , including carcinoma in situ and metastatic carcinoma . LRP5Delta was required in MCF7 breast cancer cells for the non-PHOSphorylated active beta-catenin level , transcription activity of beta-catenin , cell growth in vitro , and breast tumor growth in a xenograft SCID mouse model . WNT3 ligand , but not WNT1 and WNT3A augmented the endogenous beta-catenin activity of MCF7 cells in a DKK1-insensitive manner . Furthermore , an anti-LRP5 antibody attenuated beta-catenin activity , inhibited cell growth , and induced apoptosis in LRP5Delta-positive MCF7 and T-47D breast cancer cells , but not in control cells . Conclusions/Significance Our results suggest that the LRP5Delta receptor is strongly implicated in mammary gland tumorigenesis and that its aberrant expression present an early event during disease progression . LRP5 antibody therapy may have a significant role in the treatment of breast cancer .