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Different Mechanisms of Regulation of the Warburg Effect in Lymphoblastoid and
Burkitt Lymphoma Cells
#MMPMID26312753
Mushtaq M
; Darekar S
; Klein G
; Kashuba E
PLoS One
2015[]; 10
(8
): e0136142
PMID26312753
show ga
BACKGROUND: The Warburg effect is one of the hallmarks of cancer and rapidly
proliferating cells. It is known that the hypoxia-inducible factor 1-alpha
(HIF1A) and MYC proteins cooperatively regulate expression of the HK2 and PDK1
genes, respectively, in the Burkitt lymphoma (BL) cell line P493-6, carrying an
inducible MYC gene repression system. However, the mechanism of aerobic
glycolysis in BL cells has not yet been fully understood. METHODS AND FINDINGS:
Western blot analysis showed that the HIF1A protein was highly expressed in
Epstein-Barr virus (EBV)-positive BL cell lines. Using biochemical assays and
quantitative PCR (Q-PCR), we found that-unlike in lymphoblastoid cell lines
(LCLs)-the MYC protein was the master regulator of the Warburg effect in these BL
cell lines. Inhibition of the transactivation ability of MYC had no influence on
aerobic glycolysis in LCLs, but it led to decreased expression of MYC-dependent
genes and lactate dehydrogenase A (LDHA) activity in BL cells. CONCLUSIONS: Our
data suggest that aerobic glycolysis, or the Warburg effect, in BL cells is
regulated by MYC expressed at high levels, whereas in LCLs, HIF1A is responsible
for this phenomenon.