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The Influence of Adipogenic Progenitors and Duffy-Null Phenotype on the Normal Breast and Breast Cancer Biology of Women of African Descent
Breast cancer is African American women tend to be highly aggressive and metastatic compared to breast cancers in Caucasian women. Within African American women, those who carry inherited duffy null or heterozygous alleles show even worse outcome from breast cancer. We had previously demonstrated elevated number of PROCR+/ZEB1+/PDGFRA+ (PZP) cells in the normal breast of African American women and breast epithelial cells in duffy null/heterozygous carriers have elevated activity of cMET oncogene. In this year report, we have characterized PZP cells further and found that interaction between PZP cells and breast epithelial cells leads to elevated expression of interleukin 6, which could lead to changes in the tumor microenvironment that enhance metastasis. Similar to ZEB1+ cells, normal breast tissues of African American women express higher levels of PROCR and PDGFRA. With respect to duffy phenotype, we have generated breast epithelial cell lines from duffy heterozygous women and transformed these cell lines with HRASG12V and mutant p53. These cell lines are being characterized for growth and metastasis in vivo.
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