CBIO-01: COEXPRESSION OF FATTY ACID SYNTHASE (FASN) AND CARNITINE PALMITOYLTRANSFERASE 1C (CPT1C) IN HUMAN GLIOMAS

Otto Warburg observed that cancer cells preferentially consume glucose to produce lactic acid even under aerobic conditions. Therefore, cancer metabolism differs from normal cell metabolism. Furthermore, isocitrate dehydrogenase 1 (IDH1) and 2(IDH2), enzymes that function in the tricarboxylic acid cycle, lipid synthesis and carbohydrate use, are frequently mutated in low-grade glioma and secondary glioblastoma. Although cancer metabolism differs from normal cell metabolism, there are little researches for lipid metabolism with cancer. Fatty acid synthase (FASN) and carnitine palmitoyltransferase 1(CPT1) are related to fatty acid metabolism. Many types of tumor cells, including glioblastoma cells, show increased expression of FASN and increased level of mRNA expression of carnitine palmitoyltransferase 1C (CPT1C), which is a brain-specific isoform of CPT1. CPT1 has three isoforms, including CPT1A, CPT1B and CPT1C. CPT1A and CPT1B are associated with beta-oxidation of fatty acids in mitochondria. However, CPT1C is normally found only in the microsomal fraction of neurons, and shows a much lower carnitine acyltransferase activity than other CPT1s. Accordingly, we examined the expression and subcellular localization of FASN and CPT1C in 2 human glioma cell lines (U87MG and U373MG) and 41 surgical specimens of gliomas with various histological grades (21 with the IDH1 R132H mutation and 20 without the mutation) by immunostaining. CPT1C was mainly localized to the nuclei, whereas FASN localized to the cytoplasm, regardless of the genetic status of IDH1 and the histological grade. In conclusion, we observed that various glioma cells coexpressed CPT1C and FASN.