Both HIF-1 alpha and HK II protein expressions were co-localized in the cancer cells near necrosis, and the intensity of HIF-1 alpha protein expression was significantly correlated with HK II mRNA expression in both tumors.
Interestingly, miR-143 expression was inversely associated with HK2 protein level but not mRNA level in human lung cancer samples. miR-143, down-regulated by mammalian target of rapamycin activation, reduces glucose metabolism and inhibits cancer cell proliferation and tumor formation through targeting HK2.
As the tumorHKII promoter plays a significant role in HKII overexpression, studies reported here were undertaken to identify both the major regions and transcription factors involved under tumor-like conditions.
STRING analysis confirmed protein-protein-interactions of regulated genes and Western immunoblotting of fatty acid synthase, serine hydroxyl-methyltransferase 1, arginine 1 and hexokinase 2 showed tumor specific induction.
Increased lactate labeling in tumors correlated with c-Myc-driven expression of hexokinase 2, lactate dehydrogenase A, and the monocarboxylate transporters and was accompanied by increased radioresistance.
The HK2 silenced U87 and U251 cell lines were assessed for their proliferation, migration and invasive potential in vitro, while the tumor forming potential of U87 cells was evaluated in vivo.
We analyzed tumor cell Glut-1 and HKII mRNA expression with real-time polymerase chain reaction and Western blotting, (3)H-FDG uptake per cell, and cell viability with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay.
Human laryngeal carcinoma Hep-2 cells were stably transfected with a plasmid expressing HK2 shRNA (pGenesil-1.1-HK2) and were compared to control cells with respect to the cell cycle, cell viability, apoptosis, and their ability to form xenograft tumors.
Using cell lines and primary cultures of GBM, we showed that inducible knockdown of HK2 altered tumor metabolism, which could not be recapitulated by HK1 or HK3 loss.