Abstract A03: Tumorigenesis involving expansion of CD24 high CD61 cells is abrogated by tamoxifen in mouse models of luminal breast cancer

The cells within the mammary gland that are altered by tamoxifen chemoprevention and correlate with abrogation of tumorigenesis are unknown. We have documented that a 60 day tamoxifen chemopreventive regimen reduces tumor incidence in NRL-TGFalpha and MMTV-c-neu mouse models of luminal breast cancer. For this study our goal was to identify the aberrant and/or altered mammary cell subpopulations typically found in the mammary gland of TGFalpha and c-neu mice and determine the effect of tamoxifen on their relative quantity. Mammary cell subpopulations were evaluated using flow cytometric analysis by labeling lineage negative cells with CD24, CD61 and CD49f fluorescently tagged antibodies. TGFalpha mice developed an expanded CD24high CD61positive fraction of cells coinciding with hyperplasia and tumor presence. Prior to tumor development c-neu mice had an expanded CD24medium CD49f high cell fraction and by the time tumors developed, both nontumorous glands and tumors also displayed an expanded CD24high CD61positive cell fraction. Mammary glands from mice that received a 60 day tamoxifen chemopreventive regimen did not display expanded cell fractions compared to placebo treated mice in both models. Our data indicate that tamoxifen chemoprevention abrogates tumorigenesis that involves expansion of CD24high CD61positive cells. Further investigations into tamoxifen effects on mammary cell subpopulations is critical for a clearer understanding of the utility of tamoxifen and other estrogen receptor modulators as chemopreventives.

Citation Format: Olga Zhdankin, Melanie Bomier, Donna Parke, Jon Holy, Teresa Rose-Hellekant. Tumorigenesis involving expansion of CD24 high CD61 cells is abrogated by tamoxifen in mouse models of luminal breast cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A03.