title: Kaiso represses the expression of glucocorticoid receptor via a methylation-dependent mechanism and attenuates the anti-apoptotic activity of glucocorticoids in breast cancer cells.
abstract: 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].
authors.affiliation: Department of Clinical Biochemistry, Clinical Medicine Laboratory; Department of Anatomy Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, Hunan 410219, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Gynaecology and Obstetrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Clinical Biochemistry, Clinical Medicine Laboratory, Institute of Neuroscience, Changsha Medical University, Changsha, Hunan 410219, China.
authors.forename: Fang-Hui
authors.initials: FH
authors.lastname: Yang
authors.affiliation: Department of Clinical Biochemistry, Clinical Medicine Laboratory, Institute of Neuroscience, Changsha Medical University, Changsha, Hunan 410219, China.
authors.forename: Zi-Bo
authors.initials: ZB
authors.lastname: Li
authors.affiliation: Department of Clinical Biochemistry, Clinical Medicine Laboratory, Institute of Neuroscience, Changsha Medical University, Changsha, Hunan 410219, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Clinical Biochemistry, Clinical Medicine Laboratory, Institute of Neuroscience, Changsha Medical University, Changsha, Hunan 410219, China.
authors.forename: Xie-Hong
authors.initials: XH
authors.lastname: Liu
authors.affiliation: Department of Clinical Biochemistry, Clinical Medicine Laboratory, Institute of Neuroscience, Changsha Medical University, Changsha, Hunan 410219, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Metabolic Syndrome Research Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008745:Methylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; C492254:ZBTB33 protein, human