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Targeting Basal Breast Cancer


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Our goal was to determine 1) if Gpr identifies mammary stem and/or progenitors; 2) the significance of Gpr expression in murine and human breast tumors. We proposed to: a) identify and characterize Gpr+ cells, determine their potency by lineage tracing, assess the effect of Gpr cell ablation on mammary development; b) determine Gpr expression in human breast cancers and cell lines, and test if ablating Gpr+ cells affects mammary tumorigenesis in mouse models. In this six month grant period we have 1) identified genes that permit distinct Gpr-positive progenitor subpopulations to be identified thereby permitting their differential gene expression profiles to be compared; 2) transplanted Gpr cells to test their plasticity 3) demonstrated association of high Gpr expression with specific TNBC subsets and basal-type breast cancer cell lines; 4) reestablished the cohort of compound tumor mice that were lost due to COVID shutdown to permit ablation studies to proceed; 5) established organoid cultures to permit parallel studies in vitro. Our results to date have shown that Gpr identifies mammary stem cells in the embryo and unipotent progenitors in perinatal and postnatal mammary gland located at invasive ductal tips. Our data in this period consolidate the finding that Gpr+ is a highly specific marker of multiple distinct mammary progenitors and that high Gpr expression is associated with early tumor onset and poor outcome in the most aggressive types of breast cancer.



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