Endoxifen hydrochloride, the active metabolite of Tamoxifen, is a potent antiestrogen that targets estrogen receptor. Estrogen receptor[1]
Endoxifen blocks ER-alpha transcriptional activity and inhibits estrogen-induced breast cancer cell proliferation. These studies reveal that Endoxifen concentrations between 10 and 1000 nM enhance ERα protein degradation. Lower concentrations of Endoxifen (≤1 nM) do not affect ERα protein levels[1].
GLAST::Cre(ERT);ROSA26loxP/loxP mice are injected intraventricularly with 5 μL 5 mM Endoxifen, and mice injected with 4 μL Adeno-Cre virus [109 plaque-forming units (pfu)] serve as positive control. At 7-10 days after ICV injection, mice are sacrificed and the SVZ dissected to isolate and derive stem and progenitor cells. These stem/progenitor cells are then cultured in permissive medium to form neurospheres and assayed for recombination. In our unpassaged preparations is found derived from Endoxifen-injected GLAST::CreERT2;ROSA26loxP/loxP mice that 1.9% of neurospheres show recombination, compared to a higher rate of 4.3% of neurospheres in Adeno-Cre-recombined ROSA26loxP/loxP mice[2].
[1]. Wu X, et al. The tamoxifen metabolite, Endoxifen, is a potent antiestrogen that targets estrogen receptor alpha fordegradation in breast cancer cells. Cancer Res. 2009 Mar 1;69(5):1722-7. [2]. Benedykcinska A, et al.Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite Endoxifen. Dis Model Mech. 2016 Feb;9(2):211-20.