title: JUNB promotes the survival of Flavopiridol treated human breast cancer cells.
abstract: 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.
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH 43210, USA. Electronic address: hicks.270@osu.edu.
authors.forename: Mellissa
authors.initials: M
authors.lastname: Hicks
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH 43210, USA.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, 4th Floor, Starling Loving Hall, 320 West 10th Avenue, Columbus, OH 43210, USA. Electronic address: macrae.3@osu.edu.
authors.forename: Erin
authors.initials: E
authors.lastname: Macrae
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, OH 43210, USA. Electronic address: dewille.1@osu.edu.
authors.forename: James
authors.initials: J
authors.lastname: DeWille
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D000077157:Sorafenib; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; C581727:JunB protein, human; D010671:Phenylurea Compounds; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D014157:Transcription Factors; D009536:Niacinamide; C077990:alvocidib; D000077157:Sorafenib
keywords: CDK9; Chemotherapy resistance; Flavopiridol; JUNB; Sorafenib