Myc Regulates a Transcriptional Program That Stimulates Glutaminolysis

David R. Wise¹, Anthony Mancuso, Ralph Deberardinis², Sayed Nabil, Xiao-Yong Zhang³, Harla K. Pfeiffer³, Ilana Nissim⁴, Evgueni Daikhind⁴, Marc Yudkoff⁴, Steven B. McMahon³, Craig B. Thompson

High levels of both glucose and glutamine consumption are required for rapid proliferation of most cancer cells. In this work, the role of myc in regulating the transcriptional control of glutaminolysis was examined. Two different models were used: immortalized mouse embryo fibroblasts (MEF) with inducible myc activity and human glioma cells with naturally high myc levels that were knocked down with short-hairpin RNA. Elevated myc activity was associated with increased glutamine transport, glutaminase activity and lactate dehydrogenase activity as demonstrated by PCR. It was also associated with increased overall glutimolytic flux as evidenced by ¹³C NMR.