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The lactate dehydrogenase-A gene (\n                    <jats:italic>LDH-A<\/jats:italic>\n                    ), 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\n                    <jats:italic>LDH-A<\/jats:italic>\n                    alone or those transformed by c-Myc overproduce lactic acid.\n                    <jats:italic>LDH-A<\/jats:italic>\n                    overexpression is required for c-Myc-mediated transformation because lowering its level through antisense\n                    <jats:italic>LDH-A<\/jats:italic>\n                    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\n                    <jats:italic>LDH-A<\/jats:italic>\n                    , whose expression increases lactate production and is necessary for c-Myc-mediated transformation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.13.6658","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:39Z","timestamp":1027679499000},"page":"6658-6663","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":951,"title":["c-Myc transactivation of\n                    <i>LDH-A<\/i>\n                    : Implications for tumor metabolism\u2009and\u2009growth"],"prefix":"10.1073","volume":"94","author":[{"given":"Hyunsuk","family":"Shim","sequence":"first","affiliation":[{"name":"Departments of Medicine and Molecular Biology and Genetics, The Johns Hopkins Oncology Center, and Program in Human Genetics and Molecular Biology, The Johns Hopkins University School of 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