乳腺癌耐药是患者预后不良的重要原因。SPIN1是一种新型组蛋白“阅读器”，与肿瘤的发生发展相关，本课题组发现其在乳腺癌耐药组织中高表达，可以上调PI3K/Akt通路进而促进乳腺癌耐药。然而目前乳腺癌中SPIN1上下游调控机制有待进一步研究。前期预实验提示转录因子ETS1可结合到SPIN1的启动子区，促进其表达；而SPIN1可结合到PI3K/Akt通路调节因子EGFR的启动子区，促进其转录。本课题组推测乳腺癌中表达上调的ETS1可促进SPIN1转录，SPIN1亦可促进EGFR转录，进而激活PI3K/Akt通路，促进乳腺癌耐药。本研究拟进一步探究SPIN1及ETS1在乳腺癌中的表达及临床意义，研究其在体外、体内对乳腺癌耐药的影响，验证ETS1对SPIN1及SPIN1对EGFR的调控作用，从而构建ETS1-SPIN1-EGFR-PI3K/Akt调控网络，有望为逆转乳腺癌耐药提供新的潜在靶点。

Breast cancer resistance is an important cause of poor prognosis in patients. SPIN1 is a novel histone code “reader”, which is related to the occurrence and development of tumors. Previously we found that it was highly expressed in breast cancer drug-resistant tissues and could up-regulate PI3K/Akt pathway to promote breast cancer drug resistance. However, the upstream and downstream regulation mechanism of SPIN1 in breast cancer needs further investigation. Preliminary experiment suggests that the transcription factor ETS1 could bind to the promoter region of SPIN1 to promote its expression, while SPIN1 could bind to the promoter region of the PI3K/Akt pathway regulator EGFR and promote its transcription. We speculate that ETS1, which is up-regulated in breast cancer, could promote SPIN1 transcription, and SPIN1 could also promote EGFR transcription, thereby activating PI3K/Akt pathway and promoting breast cancer drug resistance. This study intends to further explore the expression and clinical significance of SPIN1 and ETS1 in breast cancer, investigate the effects on breast cancer drug resistance in vitro and in vivo, and verify the ETS1/SPIN1/EGFR regulation axis. The construction of the ETS1-SPIN1-EGFR-PI3K/Akt regulatory network is expected to provide new potential targets for reversing breast cancer drug resistance.