The Effects of Tamoxifen on Mammary Organoids from Young and Old MMTV-c-neu Mice

Abstract

Tamoxifen, an estrogen antagonist, can prevent ER-positive tumor development in women at risk of developing breast cancer. Mouse studies demonstrate that tamoxifen can prevent ER-negative tumors if administered to young mice. This project examined the differences in cell populations and progenitor activity between mammary organoids from young and old MMTV-c-neu mice, treated with or without tamoxifen. Tamoxifen-treatment increased the proportion of luminal, colony-forming cells in 2D but decreased the proportions of basal and CD61-positive, luminal progenitor cells in young and old mouse organoids. Tamoxifen tended to increase the proportions of CD61-negative, luminal cells in old organoids but reduced this population in young mouse organoids. In 3D cultures, tamoxifen increased the number of luminal-like colonies produced by old, but not young, mouse organoid cells. These results suggest that aging renders the CD61-negative, luminal cell population resistant to tamoxifen and that this population should be targeted for the prevention of ER-negative tumors.