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|タイトル: ||Tumor uptake of radiolabeled acetate reflects the expression of cytosolic acetyl-CoA synthetase: implications for the mechanism of acetate PET|
|著者: ||YOSHII, Yukie|
WELCH, Michael J.
|Issue Date: ||Oct-2009|
|出版者: ||ELSEVIER B.V.|
|抄録: ||Introduction: [1-^<11>C]acetate positron emission tomography (PET) is used for myocardial
studies. In the myocardium, mitochondrial acetyl-CoA synthetase (ACSS1) mainly
contributes to the radiopharmaceutical uptake. [1-^<11>C]acetate PET is also used for tumor
diagnosis; however, the uptake mechanism of radiolabeled acetate in tumors remains unclear.
Our previous study reported that cytosolic acetyl-CoA synthetase (ACSS2) was expressed in
tumor cells and up-regulated under hypoxia; whereas, expression of ACSS1 was negligible
regardless of the oxygen conditions. We also indicated that ACSS2 is a bi-directional enzyme
that controls acetyl-CoA / acetate metabolism in tumor cells. In this study, to elucidate the
basic mechanism of tumor acetate uptake, we focused on ACSS2 and investigated the role of
ACSS2 in the uptake of radiolabeled acetate in tumor cells. Methods: [1-^<14>C]acetate uptake and ACSS2 expression were examined in four tumor cell
lines under normoxia or hypoxia. An ACSS2 knockdown study was also performed.
Results: [1-^<14>C]acetate uptake was increased in the tumor cells under hypoxia. This pattern
followed that of ACSS2 expression. The incorporated ^<14>C was mostly distributed in the
lipid-soluble fractions, and this tendency increased under hypoxia. ACSS2 knock down led to
a corresponding reduction in [1-^<14>C]acetate uptake in all tumor cell lines examined under
normoxia and hypoxia. Conclusions: ACSS2 plays an important role in the uptake of radiolabeled acetate in tumor
cells, which is different from that in the myocardium, which mainly involves ACSS1. The
uptake of radiolabeled acetate in tumors increased under hypoxia along with up-regulation of
ACSS2 expression. This suggests a possible mechanism for acetate PET for tumors.|
|Appears in Collections:||07 高エネルギー医学研究センター|
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