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

Hyunsuk Shim, Christine Dolde, Brian C. Lewis, Chyi Sun Wu, Gerard Dang, Richard A. Jungmann, Riccardo Dalla-Favera, Chi V. Dang

Research output: Contribution to journalArticlepeer-review


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

Original languageEnglish (US)
Pages (from-to)6658-6663
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - Jun 24 1997


  • Hypoxia
  • Lactate dehydrogenase
  • Oncogene
  • Tumorigenicity

ASJC Scopus subject areas

  • Genetics
  • General


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