Keap1负向调控p62抑制乳腺癌增殖及分子调控机制的研究

近年来，有研究陆续报道称Keap1在乳腺癌中表达异常，但Keap1参与乳腺癌发生发展的机制尚不清楚。预实验发现：（1）Keap1在乳腺癌组织和细胞中表达降低，p62在乳腺癌组织和细胞中表达增高，并且在乳腺癌组织中Keap1与p62呈负相关；（2）Keap1抑制乳腺癌细胞的增殖，并导致p62、经典WNT信号通路中β-catenin及其下游靶蛋白cyclinD1的降低；（3）乳腺癌细胞中Keap1与p62相互结合。据此推测：Keap1直接或间接负向调控p62抑制WNT/β-catenin信号通路进而抑制乳腺癌的增殖。课题组拟首先分析Keap1与p62在乳腺癌组织中的相关关系；其次分析Keap1调节p62对WNT/β-catenin信号通路参与乳腺癌增殖作用的影响；最后分析Keap1调控p62的具体分子机制。

In recent years, some studies have reported that Keap1was expressed abnormally in breast cancer, but the mechanism of Keap1 involved in the development of breast cancer is not clear. Our preliminary studies showed that: (1) the expression of Keap1 in breast cancer tissues and cells was decreased, but the expression of p62 was increased, moreover Keap1 was negatively correlated with p62 in the breast cancer tissues; (2) Keap1 inhibited the proliferation of breast cancer cells and decreased the expressions of p62, β-catenin and its downstream target protein cyclinD1 in classical WNT signaling pathway; (3) Keap1 and p62 in breast cancer cells were combined with each other. So, we speculated that Keap1 may directly or indirectly negatively regulate p62 to inhibit the WNT/β-catenin signaling pathway.and futherly inhibit the proliferation of breast cancer. Our research group planted to analyze the correlation between Keap1 and p62 in breast cancer first and then to analyze the effect of Keap1 regulating p62 on WNT / β-catenin signaling pathway participating the proliferation of breast cancer. Finally, the specific molecular mechanism of Keap1 regulating p62 would be analyzed.