Adenine Nucleotide Translocase 2 as an Enzyme Related to [¹⁸F] FDG Accumulation in Various Cancers.

PURPOSE:Although glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) are known as major proteins involved in the molecular mechanisms for accumulating 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) in cancer cells, sometimes, [¹⁸F] FDG accumulation cannot be explained by the expression of these two proteins. We investigated the involvement of adenine nucleotide translocase 2 (ANT2), which catalyzes ADP/ATP exchange at the mitochondrial inner membrane, in [¹⁸F] FDG accumulation. PROCEDURES:ANT2 expression was evaluated in various cancer cell lines and human cancer tissues (microarrays) using western blot and immunohistochemical (IHC) staining, respectively. The expression levels of ANT2 were compared to [¹⁸F] FDG accumulation and pathologic findings, including differentiation grade. Additionally, we modulated ANT2 expression levels using ANT2 siRNA and an ANT2 expression vector in cancer cells and murine xenografted tumors. RESULTS:[¹⁸F] FDG accumulation correlated with ANT2 expression in various cancer cell lines; this was not explained by GLUT1 and/or HK2 expression. At both the cell and tissue levels, ANT2 expression was high in less-differentiated or more malignant type of cancers. [¹⁸F] FDG accumulation changed according to the modulation of the ANT2 expression level. CONCLUSION:In various cancer cells and tissues, the expression levels of ANT2 explained [¹⁸F] FDG accumulation better than those of GLUT1 and HK2. ANT2 can be used as a marker of dedifferentiated pathology and aggressiveness of cancer.

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