title: LDH-A influences hypoxia-inducible factor 1α (HIF1 α) and is critical for growth of HT29 colon carcinoma cells in vivo.
abstract: Serum lactate dehydrogenase (LDH) is a well-known clinical surrogate parameter. A high activity of LDH is associated with a poor prognosis in different tumor types. Here we demonstrate by a gene silencing approach that LDH-A is critical for in vivo but not in vitro growth of HT29 colon carcinoma cells. We provide evidence that the suppression of the LDH-A gene leads to an increased level of hypoxia inducible factor 1α (HIF1α) but in consequence not to an increase of HIF1 regulated proteins such as carbonic anhydrase IX (CAIX), vascular endothelial growth factor (VEGF), prolyl-hydroxylase 2 (PHD2), and factor-inhibiting HIF (FIH) in cell cultures and tumor lysates. This effect is independent of LDH activity in vivo. We conclude that LDH-A has an influence on the activity of HIF1α and thus on the adaptation of cells to a hypoxic tumor microenvironment in HT29 colon cells. We suggest the use of LDH-M as a potential therapeutic target for anticancer treatment.
authors.affiliation: Robert Koch-Institut, 13353, Berlin, Germany. LanghammerS@rki.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Langhammer
authors.forename: Maher
authors.initials: M
authors.lastname: Najjar
authors.forename: Holger
authors.initials: H
authors.lastname: Hess-Stumpp
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Thierauch
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D019073:HT29 Cells; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D051379:Mice; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D051793:Hypoxia-Inducible Factor 1; D007527:Isoenzymes; D034741:RNA, Small Interfering; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5