ERRalpha mediates metabolic adaptations that drive lapatinib resistance in breast cancer (ERRalpha binding profiles in breast cancer cells by ChIP-seq). Homo sapiens

Ablation of ERRalpha significantly delays ERBB2-induced mammary tumorigenesis and ERRalpha regulates genes of the ERBB2 amplicon. To further investigate the relationship between ERRalpha activity and RTK signaling, we mapped ERRalpha binding sites in SKBr3 cells upon EGF treatment or heregulin treatment. Inhibition of ERBB2 signaling using the RTK inhibitor lapatinib impacts on ERRalpha stability, while cells resistant to lapatinib treatment exhibit restored ERRalpha expression. We therefore mapped ERRalpha binding sites in parental (sensitive) cells (pSKBr3) as well as in lapatinib-resistant cells (LRSKBr3). Overall design: ChIP-Seq analysis of ERRalpha binding profile in SKBr3 or BT-474 breast cancer cells.

敲除雌激素相关受体α（ERRalpha）可显著延迟人表皮生长因子受体2（ERBB2）诱导的乳腺肿瘤发生，且ERRalpha可调控ERBB2扩增子的相关基因。为进一步探究ERRalpha活性与受体酪氨酸激酶（RTK）信号通路之间的关联，我们在经表皮生长因子（EGF）或调蛋白（heregulin）处理的SKBr3细胞中绘制了ERRalpha的全基因组结合位点图谱。使用RTK抑制剂拉帕替尼（lapatinib）抑制ERBB2信号通路会影响ERRalpha的蛋白稳定性，而对拉帕替尼产生耐药的细胞则可恢复ERRalpha的表达水平。因此，我们分别在亲本（敏感）细胞（pSKBr3）以及拉帕替尼耐药细胞（LRSKBr3）中绘制了ERRalpha的结合位点图谱。整体实验设计：对SKBr3或BT-474乳腺癌细胞中的ERRalpha结合谱进行染色质免疫沉淀测序（ChIP-Seq）分析。