Zhou Lin, Zhong Yan, Yang Fang-Hui, Li Zi-Bo, Zhou Jiang, Liu Xie-Hong, Li Min, Hu Fang
Department of Clinical Biochemistry, Clinical Medicine Laboratory; Department of Anatomy Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, Hunan 410219, China.
Department of Gynaecology and Obstetrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
BMB Rep. 2016 Mar;49(3):167-72. doi: 10.5483/bmbrep.2016.49.3.151.
Kaiso is a Pox Virus and Zinc Finger (POZ-ZF) transcription factor with bi-modal DNA-binding specificity. Here, we demonstrated that Kaiso expression is inversely correlated with glucocorticoid receptor (GR) expression in breast carcinomas. Knockdown of Kaiso increased GR expression, while overexpression of Kaiso inhibited GR expression in breast cancer cells. Furthermore, Kaiso repressed GR proximal promoter-reporter activity in a dose-dependent manner. Remarkably, ChIP experiments demonstrated that endogenous Kaiso was associated with the GR promoter sequence in a methylation-dependent manner. Since glucocorticoids inhibit chemotherapyinduced apoptosis and have been widely used as a co-treatment of patients with breast cancer, we assessed the role of Kasio in GR-mediated anti-apoptotic effects. We found that overexpression of Kaiso attenuated the anti-apoptotic effects of glucocorticoids in breast cancer cells. Our findings suggest that GR is a putative target gene of Kaiso and suggest Kaiso to be a potential therapeutic target in GC-combination chemotherapy in breast cancer. [BMB Reports 2016; 49(3): 167-172].
Kaiso是一种具有双模式DNA结合特异性的痘病毒和锌指（POZ-ZF）转录因子。在此，我们证明了Kaiso的表达与乳腺癌中糖皮质激素受体（GR）的表达呈负相关。敲低Kaiso可增加GR的表达，而在乳腺癌细胞中过表达Kaiso则抑制GR的表达。此外，Kaiso以剂量依赖的方式抑制GR近端启动子-报告基因活性。值得注意的是，染色质免疫沉淀实验表明内源性Kaiso以甲基化依赖的方式与GR启动子序列相关联。由于糖皮质激素可抑制化疗诱导的细胞凋亡，并且已被广泛用作乳腺癌患者的联合治疗药物，我们评估了Kaiso在GR介导的抗凋亡作用中的作用。我们发现过表达Kaiso可减弱糖皮质激素对乳腺癌细胞的抗凋亡作用。我们的研究结果表明GR是Kaiso的一个假定靶基因，并表明Kaiso是乳腺癌GC联合化疗中的一个潜在治疗靶点。[《BMB报告》2016年；49(3): 167 - 172]
