방사선의학 웹진

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Abstract
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.

Author information

Lee CH1,2,3,4, Kim MJ1,3,4, Lee HH1, Paeng JC1, Park YJ5, Oh SW1,6, Chai YJ7, Kim YA8, Cheon GJ1,3, Kang KW1,3, Youn H9,10,11,12, Chung JK13,14,15,16.
1
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea.
2
Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
3
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
4
Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, South Korea.
5
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
6
Department of Nuclear medicine, Seoul National University Boramae Medical Center, Seoul, South Korea.
7
Department of Surgery, Seoul National University Boramae Medical Center, Seoul, South Korea.
8
Department of Pathology, Seoul National University Boramae Medical Center, Seoul, South Korea.
9
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea. hwyoun@snu.ac.kr.
10
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. hwyoun@snu.ac.kr.
11
Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, South Korea. hwyoun@snu.ac.kr.
12
Cancer Imaging Center, Seoul National University Hospital, Seoul, South Korea. hwyoun@snu.ac.kr.
13
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea. jkchung@snu.ac.kr.
14
Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea. jkchung@snu.ac.kr.
15
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. jkchung@snu.ac.kr.
16
Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, South Korea. jkchung@snu.ac.kr.