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Reductive carboxylation and 2-hydroxyglutarate formation by wild-type IDH2 in breast carcinoma cells
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SYSNO ASEP 0446813 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Reductive carboxylation and 2-hydroxyglutarate formation by wild-type IDH2 in breast carcinoma cells Author(s) Smolková, Katarína (FGU-C) RID, ORCID, SAI
Dvořák, Aleš (FGU-C) ORCID, RID, SAI
Zelenka, Jaroslav (FGU-C) RID
Vítek, L. (CZ)
Ježek, Petr (FGU-C) RID, ORCIDSource Title International Journal of Biochemistry and Cell Biology. - : Elsevier - ISSN 1357-2725
Roč. 65, AUG 15 (2015), s. 125-133Number of pages 9 s. Language eng - English Country GB - United Kingdom Keywords reductive carboxylation ; NADPH-dependent isocitrate ; dehydrogenase IDH2 ; hypoxia ; 2-hydroxyglutarate Subject RIV FD - Oncology ; Hematology R&D Projects GPP301/12/P381 GA ČR - Czech Science Foundation (CSF) LF14001 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support FGU-C - RVO:67985823 UT WOS 000358804400013 EID SCOPUS 84930938063 DOI 10.1016/j.biocel.2015.05.012 Annotation We quantified CO2–dependent reductive carboxylation glutaminolysis (RCG) and CO2–independent 2HG production in HTB-126 and MDA-MB-231 breast carcinoma cells by measuring 13C incorporation from 1-13C-glutamine into citrate, malate, and 2-hydroxyglutarate (2HG), for which we found a substantial enrichment that ceased upon IDH2 silencing. Relatively high basal 12C-2HG levels existed (5-fold higher vs. non-tumor HTB-125 cells) and 13C-2HG was formed despite the absence of any idh2 and idh1 mutations in HTB-126 cells. Since RCG is enhanced at hypoxia (frequent in solid tumors) and 2HG can be formed without idh1/2 mutations, we suggest 2HG as an analytic marker (in serum, urine, or biopsies) predicting malignancy of breast cancer in all patients Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2016
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