近年来的研究表明，乳腺癌干细胞对传统化疗药物的抵抗被认为是乳腺癌复发的根源，因此研究乳腺癌干细胞的调控因子有着重要的意义。作为在正常细胞向恶性细胞转化所必需的原癌基因FBI-1在肿瘤发生和发展起着重要的作用，但与乳腺癌干细胞以及化疗敏感性和预后中的作用还不清楚。我们的前期研究表明，FBI-1能够调控乳腺癌干细胞的数量和性质。FBI-1可能通过招募Bmi1来影响PTEN的表达以及下游信号途径AKT/Wnt/β-Catenin。 重要的是，在阿霉素产生抗药性的细胞中，敲减FBI-1能够增强乳腺癌细胞对药物的敏感性。在此基础上，本研究拟研究FBI-1是否通过调控PTEN及下游信号途径来影响乳腺癌干细胞和阿霉素药物的敏感性。4T1细胞的荷瘤小鼠的研究可以揭示乳腺癌干细胞与M2型巨噬细胞的关系以及FBI-1对它们的调控。最后，通过临床标本的研究将揭示FBI-1与化疗敏性和预后之间的关系。

Recent studies indicate that breast cancer stem cells determine chemoresistance and breast cancer recurrence. FBI-1 which is required for cellular transformation play an important role in cancer initiation and progression, but its function in chemoresistance and outcome in breast cancer treatment is unknown. Our previous studies showed that FBI-1 regulates the properties of breast cancer stem cells and tumor metastasis. FBI-1 may recruit Bmi1 onto PTEN promoter and inhibits PTEN regulation. Importantly, FBI-1 exhibited a higher expression in doxorubicin resistant cells and knockdown of FBI-1 sensitized resistant cells to doxorubicin. Based on these data, we will investigate whether FBI-1 regulates breast cancer stem cells and chemoresistance via inhibiting PTEN expression and its downstream signaling AKT/Wnt/β-Catenin. We also will investigate the relationship between breast cancer stem cells, M2 macrophages and chemoresistance through mouse models. Finally, we will collect patient samples and investigate the relationship between FBI-1 expression and chemoresistance and outcome of breast cancer. Thus, our study will provide an important indicator of chemotherapy outcome and a potential target for overcoming cheoresistance in breast cancer treatment.