传统认为内质网糖蛋白UGT1A7（简称UG）主要参与药物代谢。前期发现：高通量芯片显示UG在两种曲妥珠单抗（TSZ）耐药细胞中均显著下调；体外沉默UG可诱导乳腺癌细胞TSZ耐药，提示UG具有抑制乳腺癌TSZ耐药新功能。进一步生物信息学分析及预实验示：UG与E-cad表达显著正相关；沉默UG可诱导乳腺癌EMT进程；文献复习显示EMT可诱导乳腺癌TSZ原发性耐药，家族同源蛋白UGT1A1低表达可诱发内质网应激（ERS）、促进EMT进程；沉默UG后ERS标志蛋白显著上调。故提出“UG表达下调诱发乳腺癌ESR、促进EMT进程、从而诱导TSZ耐药”的科学假说。本研究拟结合体内外实验及临床样本论证UG抑制TSZ耐药新功能；以ERS及EMT为切入点，设计拯救实验，阐明UG下调后诱发ERS、促进EMT、诱导TSZ耐药的分子机制。有关UG抑制乳腺癌TSZ耐药的功能机制未见报道，本研究可为乳腺癌治疗提供新思路

It is believed that endoplasmic reticulum glycoprotein UGT1A7 (UG for short) is mainly involved in drug metabolism. Early research found that high throughput chip display UG in two kinds of trastuzumab resistant cells (TSZ) were significantly reduced; In vitro silencing of UG can induce TSZ resistance in breast cancer cells, these results suggest that UG can inhibit TSZ drug resistance in breast cancer. Further bioinformatics analysis and pre experiment display that UG was positively correlated with E-cad expression; Silencing UG induces breast cancer EMT process. Literature review shows EMT can induce TSZ primary drug resistance in breast cancer、endoplasmic reticulum stress(ERS) can be induced by low expression of family homologous protein UGT1A1、promote EMT process; After UG silencing, ERS marker protein increased significantly. Therefore, it is suggested that "UG expression down-regulation induces breast cancer ESR, promote EMT process, and induce TSZ resistance". This study will combine in vivo and in vitro experiments and clinical samples to demonstrate the effect of UG on the inhibition of TSZ resistance; Taking ERS and EMT as the breakthrough point, designing rescue experiment, to elucidate the molecular mechanism of that the down-regulation of UG induce ERS, promote EMT and induce TSZ resistance. The functional mechanism of UG inhibiting breast cancer TSZ resistance has not been reported, this study can provide new ideas for the treatment of breast cancer.