DNA Ligase IV Prevents Replication Fork Stalling and Promotes Cellular Proliferation in Triple Negative Breast Cancer
LIG4 amplification in different breast cancer subtypes. (a) Results were generated from cBioPortal analysis of the METABRIC breast cancer (BRCA) dataset (accessed April 2018). LIG4 amplification is observed in 8.1% of patients with basal breast cancer (n=209), significantly more frequently compared to alterations, including amplification and deep deletions, observed in 1.3% of cases in data from breast cancer subtypes excluding basal (n=2300 patients; p<0.0001). (b) In all nonbasal BRCA patients genomic alterations in LIG4 were not associated with altered mRNA expression (n=2300, p=0.8348) whereas a positive association was detected in patients with basal BRCA (n=209, p<0.0001). Cells were transfected with a single construct siRNA targeting either Lig4 or scrambled control (NT) for 24 hr or 48 hr. Lig4 depletion was confirmed using qPCR (c, d; *p<0.05; data plotted are mean + SEM) and western blot (e: BT549, f: MDA-MB231).