LDH-A influences hypoxia-inducible factor 1α (HIF1 α) and is critical for growth of HT29 colon carcinoma cells in vivo
| Autor: | Karl-Heinz Thierauch, Holger Hess-Stumpp, Stefan Langhammer, Maher Najjar |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Colorectal cancer Transplantation Heterologous Mice Nude Cell Growth Processes Biology Transfection Mice chemistry.chemical_compound Colon carcinoma In vivo Cell Line Tumor medicine Animals Humans Gene silencing Pharmacology (medical) Gene Silencing RNA Small Interfering Gene L-Lactate Dehydrogenase medicine.disease Molecular biology Up-Regulation Gene Expression Regulation Neoplastic Isoenzymes Vascular endothelial growth factor Oncology Hypoxia-inducible factors chemistry Anticancer treatment Colonic Neoplasms Hypoxia-Inducible Factor 1 Lactate Dehydrogenase 5 HT29 Cells |
| Zdroj: | Targeted Oncology. 6:155-162 |
| ISSN: | 1776-260X 1776-2596 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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