Identificationof novel diagnostic and therapeutic factors for endocrine therapy-resistant breast cancer by next-generation sequencing strategy

为了寻找新的内分泌治疗耐药乳腺癌的诊断和治疗因子，我们以FOXP 1（叉头转录因子家族之一）为候选基因，采用新一代测序技术检测其在ERα阳性乳腺癌MCF-7细胞中的全基因组分布。我们发现雌激素刺激的MCF-7细胞中FOXP 1的大部分结合区域与Erα和FOXA 1的结合区域重叠。我们还证明了FOXP 1和FOXA 1的双阳性免疫反应性与接受他莫昔芬辅助治疗的乳腺癌患者的生存预后良好显著相关。在本研究中，我们发现，与FOXA 1类似，FOXP 1被认为是Erα信号传导的关键转录因子，并且这两个叉头转录因子都可以作为乳腺癌获得性内分泌抵抗的预测因子。

To identify the novel diagnostic and therapeutic factors for endocrine therapy-resistant breast cancer, we focused on FOXP1, one of a forkhead transcription factor family, as a candidate, and its genome-wide distributionin ERα-positive breast cancer MCF-7 cells was examined by next-generation sequencing strategy. We demonstrated that majority of binding regions of FOXP1 in MCF-7 cells stimulated with estrogen were overlapped with those of both Erαand FOXA1. We also demonstrated that the double-positive immunoreactivities of FOXP1 and FOXA1 are significantly associated with a favorable prognosis for survival of breast cancer patients receiving adjuvant tamoxifen therapy. In this study, we revealed that, similar to FOXA1, FOXP1 is assumed to be a critical transcription factor for Erαsignaling, and both forkhead transcription factors can serve as predictive factors for acquired endocrine resistance in breast cancer.