Fig. 1

Expression of EZH2^T416D mutant in mammary gland develops basal-like tumors. a Representative photos of the primary and lung metastatic tumors (left panel) and images of H&E staining of the tumor tissue. b, c Representative images of IHC staining of the tumors from the primary tumors of different genotypes of GEMMs. Antibodies against CK18 and CK14, the luminal and basal-like lineage marker, were used for staining, the tumor slides from Tg-Neu, p53^f/−;Braca1^f/f;LGB-Cre, and Tg-C3 mice were used for luminal and basal-like positive control, respectively. d Kaplan–Meier overall survival curves of Tg-EZH2^WT, Tg-Neu, Tg-EZH2^T416D, and double transgenic Tg-EZH2^WT;Neu and Tg-EZH2^T416D;Neu mice. *not significant; ***p < 0.001; ****p < 0.0001, Long-rank test. e, f Expression of EZH2^T416D mutant in mammary epithelial cells downregulates luminal but upregulates basal-like marker proteins in the primary tumors. GATA3 and ERα in the primary tumor cell cultures e, and E-cadherin (E-Cad), EpCAM, and SMAα f in the whole-cell lysates from different genotypes of the GEMMs were immunoblotted with indicated specific antibodies; g, h conditional deletion of one-allele EZH2 in mammary gland partially reverses basal-like phenotypes of the tumor tissues. g Representative images of lineage marker IHC staining of the primary tumor tissue sections from the mammary tumor tissues of p53^+/f;Brca1^f/f; LGB-Cre without or with one-allele depletion of EZH2; h whole-cell lysates from primary tumors with genotypes of p53^+/−;Brca1^–/−; and p53^+/−;EZH2^+/− were immunoblotted with specific antibodies as indicated. Scale bar, 20 μm. Source data are provided as a Source Data file.