JUNB promotes the survival of Flavopiridol treated human breast cancer cells.
Chemotherapy resistance is a major obstacle to achieving durable progression-free-survival in breast cancer patients. Identifying resistance mechanisms is crucial to the development of effective breast cancer therapies. Immediate early genes (IEGs) function in the initial cellular reprogramming response to alterations in the extracellular environment and IEGs have been implicated in cancer cell development and progression. The purpose of this study was to investigate the influence of kinase inhibitors on IEG expression in breast cancer cells. The results demonstrated that Flavopiridol (FP), a CDK9 inhibitor, effectively reduced gene expression. FP treatment, however, consistently produced a delayed induction of JUNB gene expression in multiple breast cancer cell lines. Similar results were obtained with Sorafenib, a multi-kinase inhibitor and U0126, a MEK1 inhibitor. Functional studies revealed that JUNB plays a pro-survival role in kinase inhibitor treated breast cancer cells. These results demonstrate a unique induction of JUNB in response to kinase inhibitor therapies that may be among the earliest events in the progression to treatment resistance.
['Hicks|Mellissa|M|', 'Hu|Qiuping|Q|', 'Macrae|Erin|E|', 'DeWille|James|J|']
D000970:Antineoplastic Agents D001943:Breast Neoplasms D045744:Cell Line, Tumor D002470:Cell Survival D019008:Drug Resistance, Neoplasm D005260:Female D005419:Flavonoids D006801:Humans D009536:Niacinamide D010671:Phenylurea Compounds D010880:Piperidines D047428:Protein Kinase Inhibitors D000077157:Sorafenib D014157:Transcription Factors D016896:Treatment Outcome
JUNB Flavopiridol Chemotherapy resistance CDK9 Sorafenib