Dexamethasone Induces KLF5Expression In Triple Negative Breast Cancer Cell Line To Resist Chemotherapeutic Agents

Objective:To investigate the effect of Dexamethasone-induced transcription factor KLF5expression and the mechanism of resistance to chemotherapeutic agents in triple negative breast cancer cell lines (HCC1937), providing novel scientific basis for diagnosis and treatment in breast cancer.Methods:1. Western Blot detects Dexamethasone-induced the expression of KLF5in triple negative breast cancer cell line HCC1937and immortalized breast epithelial cell lines MCF10A.2. SRB assays Dexamethasone-induced triple negative breast cancer cell lines (HCC1937) sensitivity to chemotherapy agents Doxetaxel and Cisplatin.3. Western Blot detects the antagonistic effect of glucocorticoid receptor-mifepristone on the expression of KLF5in HCC1937cell lines.4. Use real-time PCR to detect the expression of KLF5at mRNA level by regulation ofGR.5. Establish pc-DNA3.1-GR plasmids and use Luciferase Report Assay to detect the expression of KLF5that regulated by glucocorticoid receptor at transcriptional level.Results:1. Transcription factor KLF5highly expresses in triple negative breast cancer cell lines HCC1937. 2. Dexamethasone/Hydrocortisone induces KLF5expression in HCC1937and MCF10A.3. Mifepristone blocks high expression of KLF5that induced by Dexamethasone in HCC1937and MCF10A, and reduces KLF5expression.4. Dexamethasone induces the regulation of GR to KLF5promoter activity at transcription level.5. Joint using breast cancer chemotherapeutic agents (Doxetaxel and Cisplatin) with Dexamethasone will reduce the sensitivity of triple-negative breast cancer cell lines (HCC1937) to chemotherapy.Conclusion:This research demonstrates that triple negative breast cancer (HCC1937) increases the resistance to chemotherapeutic agents (Doxetaxel and Cisplatin) by Dexamethasone induced KLF5highly expression, that mechanism may be relevant to the regulation of GR to KLF5promoter at transcription level.