Lactate Dehydrogenase A (LDH‐A) May Not Be Primarily Responsible for Maintaining High Tumor Lactic Acid Levels in Aggressive Breast Cancer
In: The FASEB Journal ; volume 30, issue S1 ; ISSN 0892-6638 1530-6860, 2016
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Zugriff:
A well‐known characteristic of tumor cells is the propensity to produce excessive amounts of lactic acid when deprived of normal levels of oxygen, and also when exposed to normal oxygen levels, also referred to as the Warburg effect. High levels of lactate are believed to be associated with elevated expression of lactate dehydrogenase A (LDHA), a protein up‐regulated in diverse aggressive malignancies. In this study, shRNAs were used to permanently knock down the expression of LDHA in human MDA‐MB 231 and MDA‐MB 468 cells. LDHA knockdown was confirmed by both Western Blot and qPCR. Furthermore, metabolic analysis included assessment of changes in cell viability, glucose utilization, lactate levels and cellular energy production by quantification of ATP. Silencing of the LDHA gene and protein had no effect on lactate production, glucose utilization, cellular metabolic activity and ATP in MDA‐MB 231 and MDA‐MB 468 tumor cells. These findings show no relationship between LDH‐A expression in both cells lines examined and production of lactate, nor is there any correlation to changes in the way glucose is utilized to produce ATP. The results obtained with the MDA‐MB 468 cell line confirm data previously obtained with the MDA‐MB 231 cell line. The data also suggest that cells readily adapt to knockdown conditions to continue their normal metabolic activities. Further analysis will require genomic profiling to discover shifts in gene expression that are responsible for this sustained production of lactate. Support or Funding Information Supported by grants from the National Institute on Minority Health and Health Disparities, NIMHD G12 MD007582 and P20 MD006738.
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Lactate Dehydrogenase A (LDH‐A) May Not Be Primarily Responsible for Maintaining High Tumor Lactic Acid Levels in Aggressive Breast Cancer
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Autor/in / Beteiligte Person: | Mack, Nzinga ; Mazzio, Elizabeth ; Soliman, Karam ; National Institute on Minority Health and Health Disparities |
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Zeitschrift: | The FASEB Journal ; volume 30, issue S1 ; ISSN 0892-6638 1530-6860, 2016 |
Veröffentlichung: | Wiley, 2016 |
Medientyp: | academicJournal |
DOI: | 10.1096/fasebj.30.1_supplement.698.1 |
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