DNA Ligase IV Prevents Replication Fork Stalling and Promotes Cellular Proliferation in Triple Negative Breast Cancer

Figure 1

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).

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