The Impact of Ethnicity Dependent Differences in Breast Epithelial Hierarchy on Tumor Incidence and Characteristics
Abstract
The incidence of the most aggressive triple negative breast cancer (TNBC) is significantly higher in African American (AA) than Caucasian (CA) women suggesting that the biology of the normal breasts between these two ethnic groups differ, which may contribute to altered susceptibility to tumor initiation, progression and/or metastasis. To address this hypothesis, we generated immortalized cell lines from healthy breast tissues of AA, CA and Hispanic women and characterized these cells lines for intrinsic subtypes by RNA-seq and PAM50. Based on characteristics of transformed counterparts of these cell lines, we propose that while cell type origin determines the subtype of tumor, genomic aberrations determine response to chemotherapy. We have identified an unique population of cells called PZP cells(PROCR+/ZEB1+/PDGFRalpha ) that surround the ducts and transdifferentiate into multiple cell types including fibroblasts, epithelial cells, adipocytes, and through crosstalk with epithelial cells, create a pro-inflammatory environment. PZP cells are elevated in the normal breasts of AA women and thus provide an aggressive environment for tumors to grow.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2019
- Accession Number
- AD1106068
Entities
People
- Brijesh Kumar
- Harikrishna Nakshatri
- Mayuri Prasad
Organizations
- Indiana University School of Medicine