Fig. 9.

Ezh2 silencing or inhibition inhibits ErbB2 + mammary tumor cell growth. a Ezh2 expression was silenced in an established ErbB2-driven breast cancer cell line derived from the NIC model using lentiviral shRNA (pLKO.1 shEZH2(21)) and pLKO.1 shEZH2(107). An shRNA targeting GFP was used as a negative control. Top panel shows a representative cell growth assay (mean ± SEM, ** = p < 0.01; One-way ANOVA with Dunnett’s post-test). Bottom panel is a representative immunoblot showing silencing of Ezh2. b Cells as in a were injected into the mammary fat pads of athymic nude (NCr) mice. Tumor outgrowth was monitored by palpation and caliper measurement. c Upper panel shows proliferation of ErbB2-positive MMTV-NIC breast cancer cell lines treated with the EZH2 inhibitors GSK126 and EPZ6438 (n = 4 cell lines derived from independent tumors, DMSO vs. GSK126, p = 0.038; DMSO vs. EPZ6438, p = 0.029; one-way ANOVA with Tukey’s post-test). Lower panel is a representative immunoblot showing inhibition of H3K27 tri-methylation. d Schematic diagram illustrating c-Src-dependent regulation of PRC2 components via modulation of OXPHOS and mRNA translation