c-Myc transactivation of LDH-A: Implications for tumor metabolism and growth

摘要: Cancer cells are able to overproduce lactic acid aerobically, whereas normal undergo anaerobic glycolysis only when deprived of oxygen. Tumor aerobic was recognized about seven decades ago; however, its molecular basis has remained elusive. The lactate dehydrogenase-A gene (LDH-A), whose product participates in and is frequently increased human cancers, identified as a c-Myc-responsive gene. Stably transfected Rat1a fibroblasts that overexpress LDH-A alone or those transformed by c-Myc acid. overexpression required for c-Myc-mediated transformation because lowering level through antisense expression reduces soft agar clonogenicity c-Myc-transformed fibroblasts, lymphoblastoid cells, Burkitt lymphoma cells. Although did not affect the growth adherent culture dishes under normoxic conditions, these hypoxia reduced. These observations suggest an spheroid cell mass, which hypoxic internal microenvironment. Our studies have linked induction LDH-A, increases production necessary transformation.