Tamoxifen-associated endometrial tumors expose differential enhancer activity for Estrogen Receptor alpha [Microarray Expression]. Homo sapiens

Tamoxifen, a small molecule inhibitor that binds the Estrogen Receptor alpha (ERα), blocks breast cancer progression while increasing the risk for endometrial cancer. In this study, we assessed genome-wide ERα-chromatin interactions in surgical specimens of endometrial tumors from patients who were previously treated for breast cancer with tamoxifen, and endometrial tumors from patients who were treated without tamoxifen. We compared ERα and signal at differential ERα sites in endometrial tumors of nine patients who received tamoxifen with endometrial tumors with six patients who never used tamoxifen. In addition, we performed H3K27ac (a marker for activity) ChIPs on the above mentioned endometrial tumors, and assed this signal at differential ERα sites. Compared to endometrial tumors of non-users, tamoxifen-associated endometrial tumors exposed higher H3K27ac intensities at ERα sites that are enriched in tamoxifen-associated endometrial tumors. Four tamoxifen-associated endometrial tumors that we used in our analysis have been previously published as Tumor A, B, D, and E in GSE81213. Overall design: Gene expression profiling in 111 endometrial tumors

他莫昔芬（Tamoxifen）是一种可结合雌激素受体α（Estrogen Receptor alpha, ERα）的小分子抑制剂，能够抑制乳腺癌进展，但同时会升高子宫内膜癌的发病风险。本研究针对两类子宫内膜肿瘤手术标本开展全基因组ERα-染色质互作分析：一类来自曾接受他莫昔芬治疗乳腺癌的患者，另一类来自未接受他莫昔芬治疗的患者。我们比较了9名他莫昔芬暴露患者与6名从未使用过他莫昔芬患者的子宫内膜肿瘤中，差异ERα结合位点处的ERα信号强度。此外，我们对上述子宫内膜肿瘤进行了H3K27ac（一种染色质活性标记物）染色质免疫共沉淀（ChIP）实验，并检测了差异ERα结合位点处的H3K27ac信号。与未使用他莫昔芬患者的子宫内膜肿瘤相比，他莫昔芬相关子宫内膜肿瘤在自身富集的ERα结合位点处，呈现出更高的H3K27ac信号强度。本分析中使用的4份他莫昔芬相关子宫内膜肿瘤标本，此前已作为肿瘤A、B、D、E发表于GSE81213数据集。整体实验设计：对111份子宫内膜肿瘤标本进行基因表达谱分析。