Fig. 1

Estrogen promotes Brca1-deficient mammary tumor initiation and progression. a Representative H.E staining of regenerated p18^−/−;Brca1^MGKO mammary tumors treated with or without E2. Note that the metastasized tumors in lung and liver and the highly heterogeneous tumor cell types in E2-treated mammary tumors. Boxed areas, a, b, c, and d, are enlarged to show the four different group of cells in E2-treated tumors. Spindle cells (black arrows), cells with high nuclear-cytoplasm ratio (green arrows), and mitotic cells (red arrows) are indicated. b p18^−/−;Brca1^MGKO mammary tumor cells were analyzed by tumorsphere formation assay in the presence of E2, 4OHT, dimethyl sulfoxide (DMSO), or E2 + 4OHT. The number of spheres large than 30 μm was quantified; *p < 0.05 between the E2-treated group and DMSO-treated group; **p < 0.05 between the group treated with E2 + 4OHT and the 4OHT-treated group. c BRCA1 mutant patient-derived xenograft (PDX) tumors were transplanted into the mammary fat pads of NSG mice along with E2 pellets or placebo pellets under the skin. Tumor size was measured and plotted after 4 weeks of transplantation. Data are represented as mean ± SD for tumors in each group (n = 3). d Representative H.E staining of BRCA1 mutant PDX tumors treated with or without E2. Note the clear boundary between placebo-treated tumor tissue and surrounding tumor-free tissue (left), and the E2-treated tumor front (indicated by arrows) invading the surrounding muscle tissue (right)