Targeting Basal Breast Cancer
Technical Report,01 Sep 2018,31 Aug 2019
New York University School of Medicine New York United States
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We set out to determine if 1 Gpr specifically identifies mammary stemprogenitors that expand in basal type tumors, and 2 whether ablating Gpr cells would eradicate tumors. To test these hypotheses, we proposed to a identify, isolate and characterize Gpr cells, determine their potency by tracing their progeny, and monitor the effects of ablating them on mammary development b determine Gpr expression in human breast cancer, and test if ablating Gpr cells affects mammary tumorigenesis in mouse models. In this grant period we crossed a mouse where the Gpr promoter drives expression of a tamoxifen induced cre recombinase to an inducible R26R-TdTomato reporter line, and used their progeny to trace the Gpr lineage in 1 pubertal and mature mammary ducts, 2 in ducts and alveoli during pregnancy 3 in the lactating gland and 4 in aged and multiparous mice. The results show that Gpr cells are long-lived unipotent basal stem cells during normal postnatal mammary development. 5 We have also traced the progeny of Gpr cells in MMTV-Wnt1 tumors and shown that they have acquired bipotency, generating both basal and luminal progeny, within the context of hyperplasia.
- Medicine and Medical Research