GSE155570 Short term (16 hour) treatment of ER+ breast cancer cell lines with low doses of CDK4/6 inhibition

Contributors : Andrea M Pesch ; Benjamin C Chandler ; Anna R Michmerhuizen ; Christina L Gersch ; Jose M Larios ; Corey W Speers ; James M RaeSeries Type : Expression profiling by arrayOrganism : Homo sapiensCyclin-dependent kinase 4/6 (CDK4/6) inhibitors have improved progression free survival for metastatic, estrogen receptor positive (ER+) breast cancers, but their role in the non-metastatic setting remains unclear. We sought to understand the effects of CDK4/6 inhibition (CDK4/6i) and radiation (RT) in multiple preclinical breast cancer models. Transcriptomic and proteomic analyses were used to identify significantly altered pathways after CDK4/6i. Clonogenic assays were used to quantify the RT enhancement ratio (rER). DNA damage was quantified using γH2AX staining and the neutral comet assay. DNA repair was assessed using RAD51 foci formation and non-homologous end joining (NHEJ) reporter assays. Orthotopic xenografts were used to assess the efficacy of combination therapy. Palbociclib significantly radiosensitized multiple ER+ cell lines at l ow nanomolar, sub IC50 concentrations (rER: 1.21 – 1.52) and led to a decrease in the surviving fraction of cells at 2 Gy (p< 0.001). Similar results were observed in ribociclib- (rER: 1.08 - 1.68) and abemaciclib-treated (rER: 1.19 - 2.05) cells. Combination treatment decreased RAD51 foci formation (p< 0.001), leading to a suppression of HR activity, but did not affect NHEJ efficiency (p> 0.05). Immortalized breast epithelial c...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research