Long-term E2 causes signet ring cell loss. a 3D Matrigel cultures of BCK4 cells were treated 7–20 days with vehicle, E2 alone, or E2 plus tamoxifen (Tam). In one set of 7 or 10 day E2 treated colonies, E2 was withdrawn (E2WD) for 3 to 10 days. Five fields were quantified for each sample. Signet ring cells were quantified as the percent of total cells. * p < 0.05; **p < 0.01; ***p < 0.001. b BCK4 tumor xenografts, MBCPure and the MUC and ILC regions of MBCMixed, were assayed for signet ring cells. Five fields were quantified per tumor