Targeting Basal Breast Cancer
Abstract
We set out to 1) determine if Gpr identifies mammary stem cells and progenitors; 2) test the significance of Gpr expression in murine and human breast tumors. We proposed to: a) identify and characterize Gpr+ cells, determine their lineage, assess the effect of Gpr loss or cell ablation on mammary development; b) determine Gpr expression in human breast cancers and cell lines, and test the effect of Gpr+ cell ablation on mammary tumorigenesis. We have 1) defined timing and location of Gpr mRNA and protein expression during embryonic, pubertal and adult mammary development by qPCR and lacZ reporter analyses, 2) generated ADGRA3cre knock out (KO) mice, documented their mammary and eye defects and demonstrated a requirement for the Gpr cytoplasmic and transmembrane domains, 3) traced the Gpr lineage inAdgra3cre;R26R-TdTomato mice and MMTV-Wnt1 mammary tumors, showing that Gpr marks mammary stem cells in the embryo, long-lived unipotent basal progenitors in perinatal and postnatal mammary gland and bipotent progenitors in theregenerative or tumor setting. 4) mined in silico data to show that Gpr is highly expressed in basal breast cancer and that its highest expression correlates with poor survival within this group. Our data reveal 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2021
- Accession Number
- AD1212042
Entities
People
- Pamela Cowin
Organizations
- New York University