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 journalArticle

Abstract

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
Volume94
Issue number13
DOIs
StatePublished - Jun 24 1997

Keywords

  • Hypoxia
  • Lactate dehydrogenase
  • Oncogene
  • Tumorigenicity

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'c-Myc transactivation of LDH-A: Implications for tumor metabolism and growth'. Together they form a unique fingerprint.

  • Cite this

    Shim, H., Dolde, C., Lewis, B. C., Wu, C. S., Dang, G., Jungmann, R. A., Dalla-Favera, R., & Dang, C. V. (1997). c-Myc transactivation of LDH-A: Implications for tumor metabolism and growth. Proceedings of the National Academy of Sciences of the United States of America, 94(13), 6658-6663. https://doi.org/10.1073/pnas.94.13.6658