Characterization of the AR cistrome in ER-negative breast cancer cell lines

Although molecular apocrine and some triple negative breast cancer tumours express high levels of AR, how AR signalling impacts their proliferative rate remains an area of controversy. The precise molecular mechanisms by which the AR can induce divergent proliferative effects in estrogen receptor-negative breast cancers has not been described. The potent androgen, DHT, inhibits proliferation of the MFM-223 estrogen receptor-negative breast cancer cell line. In contrast, activation of the AR by DHT either stimulates, or has no effect, on MDA-MB-453 cell proliferation. The AR cistrome was examined in order to identify candidate factors which mediate oncogenic versus tumour suppressive AR activity in ER-negative breast cancer. Two cell line models of estrogen receptor-negative breast cancer; MDA-MB-453 and MFM-223; were cultured in steroid-deplete conditions and treated for 4 hours with either a vehicle (0.001% ethanol) or 10 nM DHT. Three replicate AR ChIP-seq experiments were performed, each corresponding to independent and consecutive passages of cells. One input file is provided for each cell line. Peak files are provided for each replicate, and one bigwig file is provided for each treatment, corresponding to a merge of the data from all 3 replicates.

尽管分子顶泌型乳腺癌及部分三阴性乳腺癌肿瘤可高表达雄激素受体（Androgen Receptor, AR），但AR信号转导如何影响其增殖速率仍存在争议。目前尚未阐明AR在雌激素受体阴性乳腺癌中诱导不同增殖效应的确切分子机制。
强效雄激素双氢睾酮（Dihydrotestosterone, DHT）可抑制MFM-223雌激素受体阴性乳腺癌细胞系的增殖。与之相反，DHT激活AR则可促进或不影响MDA-MB-453细胞的增殖。
为鉴定介导雌激素受体（Estrogen Receptor, ER）阴性乳腺癌中AR致癌与抑癌活性的候选因子，研究人员对AR顺反组（cistrome）展开了分析。本研究选用两种雌激素受体阴性乳腺癌细胞系模型——MDA-MB-453与MFM-223，在类固醇剥夺培养条件中培养后，分别以溶剂对照（0.001%乙醇）或10 nM双氢睾酮处理4小时。
共开展3次独立的AR染色质免疫共沉淀测序（Chromatin Immunoprecipitation sequencing, ChIP-seq）实验，每一次实验均对应细胞的独立连续传代样本。每条细胞系均提供一份输入对照样本文件；每个生物学重复均提供峰文件，且每种处理条件均提供一份bigwig格式文件，该文件整合了全部3次重复的测序数据。