Reductive carboxylation and 2-hydroxyglutarate formation by wild-type IDH2 in breast carcinoma cells

0446813 - FGÚ 2016 RIV GB eng J - Článek v odborném periodiku
Smolková, Katarína - Dvořák, Aleš - Zelenka, Jaroslav - Vítek, L. - Ježek, Petr
Reductive carboxylation and 2-hydroxyglutarate formation by wild-type IDH2 in breast carcinoma cells.
International Journal of Biochemistry and Cell Biology. Roč. 65, AUG 15 (2015), s. 125-133. ISSN 1357-2725. E-ISSN 1878-5875
Grant CEP: GA ČR(CZ) GPP301/12/P381; GA MŠMT(CZ) LF14001
Institucionální podpora: RVO:67985823
Klíčová slova: reductive carboxylation * NADPH-dependent isocitrate * dehydrogenase IDH2 * hypoxia * 2-hydroxyglutarate
Kód oboru RIV: FD - Onkologie a hematologie
Impakt faktor: 3.905, rok: 2015

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
Trvalý link: http://hdl.handle.net/11104/0248780