Journal
BMB REPORTS
Volume 49, Issue 3, Pages 167-172Publisher
KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
DOI: 10.5483/BMBRep.2016.49.3.151
Keywords
Breast cancer; Epigenetics; Glucocorticoid receptor; Kaiso
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Funding
- Outstanding Youth Research Foundation of Education Bureau of Hunan Province, China [2011B017]
- National Natural Science Foundation of China [81300503]
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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 chemotherapy-induced 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.
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