Targeting Basal Breast Cancer
Abstract
We set out to determine if 1) Gpr specifically identifies mammary stem/progenitors 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2019
- Accession Number
- AD1093466
Entities
People
- Pamela Cowin
Organizations
- Grossman School of Medicine