Crosstalk between PARP-1 and NF-κB signaling pathways as a potential determinant of PARPi sensitivity in trastuzumab resistant HER2+ breast cancer cell lines.

606 Background: We have previously found that HER2+ breast cancer cells, despite being DNA repair proficient, are sensitive to poly (ADP-Ribose) polymerase inhibitors (PARPi). In this study, we investigated whether PARPi susceptibility would be retained in HER2+ breast cancer cells that are resistant to the HER2 targeted agent trastuzumab. Methods: Human HER2+ breast cancer cell lines BT-474, UACC812, SKBR3 and their trastuzumab resistant counterparts were used in this study. Cells were treated with vehicle or 10µM ABT-888 or transfected with scrambled or PARP-1 siRNA. We assessed cell survival by colony formation assays. Western blot analysis was used to measure protein expression. Cell cycle distribution was evaluated by propidium iodide and measured by flow cytometry. NF-κB transcriptional activity was determined via a NF-κB-driven luciferase reporter assay. The nCounter Gene Expression Assay along with qRT-PCR were used to measure the expression levels of NF-κB target genes. Tumor growth delay was ass...