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

Chul Hee Lee, Mi Jeong Kim, Hwan Hee Lee, Jin Chul Paeng, Young Joo Park, So Won Oh, Young Jun Chai, Young A Kim, Gi Jeong Cheon, Keon Wook Kang, Hyewon Youn, June Key Chung

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)722-730
Number of pages9
JournalMolecular Imaging and Biology
Volume21
Issue number4
DOIs
StatePublished - 15 Aug 2019

Fingerprint

ATP Translocases Mitochondrial ADP
Fluorodeoxyglucose F18
Enzymes
Neoplasms
Hexokinase
Facilitative Glucose Transport Proteins
Cell Line
Mitochondrial Membranes
Adenosine Diphosphate
Small Interfering RNA
Proteins

Keywords

  • Adenine nucleotide translocase 2 (ANT2)
  • Differentiation of cancer
  • GLUT1
  • HK2
  • [F]FDG-PET

Cite this

@article{b6ac3dac56f34bc3a549beaa066c4c51,
title = "Adenine Nucleotide Translocase 2 as an Enzyme Related to [18F] FDG Accumulation in Various Cancers",
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.",
keywords = "Adenine nucleotide translocase 2 (ANT2), Differentiation of cancer, GLUT1, HK2, [F]FDG-PET",
author = "Lee, {Chul Hee} and Kim, {Mi Jeong} and Lee, {Hwan Hee} and Paeng, {Jin Chul} and Park, {Young Joo} and Oh, {So Won} and Chai, {Young Jun} and Kim, {Young A} and Cheon, {Gi Jeong} and Kang, {Keon Wook} and Hyewon Youn and Chung, {June Key}",
year = "2019",
month = "8",
day = "15",
doi = "10.1007/s11307-018-1268-x",
language = "English",
volume = "21",
pages = "722--730",
journal = "Molecular Imaging and Biology",
issn = "1536-1632",
publisher = "Springer New York",
number = "4",

}

Adenine Nucleotide Translocase 2 as an Enzyme Related to [18F] FDG Accumulation in Various Cancers. / Lee, Chul Hee; Kim, Mi Jeong; Lee, Hwan Hee; Paeng, Jin Chul; Park, Young Joo; Oh, So Won; Chai, Young Jun; Kim, Young A; Cheon, Gi Jeong; Kang, Keon Wook; Youn, Hyewon; Chung, June Key.

In: Molecular Imaging and Biology, Vol. 21, No. 4, 15.08.2019, p. 722-730.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Adenine Nucleotide Translocase 2 as an Enzyme Related to [18F] FDG Accumulation in Various Cancers

AU - Lee, Chul Hee

AU - Kim, Mi Jeong

AU - Lee, Hwan Hee

AU - Paeng, Jin Chul

AU - Park, Young Joo

AU - Oh, So Won

AU - Chai, Young Jun

AU - Kim, Young A

AU - Cheon, Gi Jeong

AU - Kang, Keon Wook

AU - Youn, Hyewon

AU - Chung, June Key

PY - 2019/8/15

Y1 - 2019/8/15

N2 - 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.

AB - 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.

KW - Adenine nucleotide translocase 2 (ANT2)

KW - Differentiation of cancer

KW - GLUT1

KW - HK2

KW - [F]FDG-PET

UR - http://www.scopus.com/inward/record.url?scp=85053559008&partnerID=8YFLogxK

U2 - 10.1007/s11307-018-1268-x

DO - 10.1007/s11307-018-1268-x

M3 - Article

VL - 21

SP - 722

EP - 730

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

SN - 1536-1632

IS - 4

ER -