本项目探讨了转录辅激活因子AIB1在胆管癌发生发展中的作用及相关分子机制。通过检测AIB1在胆管癌临床样品及胆管癌细胞株中的表达情况,发现AIB1在50%的胆管癌癌变组织及细胞株中高表达。进一步通过分子生物学技术对胆管癌细胞株中AIB1进行沉默或过表达,发现AIB1在胆管癌细胞的增殖、对化疗药物的耐受及侵袭等方面具有重要的调控作用。通过对相关机制的研究发现,AIB1可通过提高Akt信号通路的活性来促进细胞的增殖并抑制细胞的凋亡;同时AIB1可作为转录因子Nrf2的辅激活因子来促进Nrf2的转录活性并促进下游靶基因(GPx2、GCLC、GCLM、ABCC2及ABCG2)的表达,从而抑制了细胞内活...Transcriptional coactivator amplified in breast cancer 1 (AIB1) plays important roles in the progression of several cancers. However, its role in Cholangiocarcinoma (CCA), a chemoresistant bile duct carcinoma with a poor prognosis, remains unclear. AIB1 protein is frequently overexpressed in human CCA specimens and CCA cell lines. Down-regulation of AIB1 induces the G2/M arrest and decreases the e...学位:博士后院系专业:生命科学学院生物医学科学系_细胞生物学学号:BH170022