title: Elevated expression of fatty acid synthase and nuclear localization of carnitine palmitoyltransferase 1C are common among human gliomas.
abstract: Fatty acid synthase (FASN) and carnitine palmitoyltransferase 1C (CPT1C), a brain-specific isoform of the CPT1 family, are upregulated in certain types of cancers, including gliomas. Acetyl-CoA carboxylase (ACC) catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis, and its phosphorylated form inhibits lipid synthesis. We examined the expression and subcellular localization of these fatty acid metabolism-related molecules in human gliomas. We performed immunostaining of two glioma cell lines (U373MG and U87MG) and 41 surgical specimens of diffuse gliomas with various histological grades (21 with the isocitrate dehydrogenase 1(IDH1) R132H mutation and 20 without the mutation). In the cultured glioma cells, CPT1C and phosphorylated ACC (p-ACC) were mainly localized to the nuclei, whereas FASN localized to the cytoplasm. In the surgical specimens, most glioma tissues showed nuclear staining for CPT1C and p-ACC, and cytoplasmic staining for FASN, regardless of the genetic status of IDH1 and the histological grade. Therefore, elevated cytoplasmic expression of FASN and nuclear localization of CPT1C are common among human diffuse gliomas, which may be regulated by the differential phosphorylation status of ACC in the cellular compartment.
authors.affiliation: Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tomihiro
authors.initials: T
authors.lastname: Wakamiya
authors.forename: Satoshi O
authors.initials: SO
authors.lastname: Suzuki
authors.forename: Hideomi
authors.initials: H
authors.lastname: Hamasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Mizoguchi
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Toru
authors.initials: T
authors.lastname: Iwaki
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology*; D002334:Carnitine O-Palmitoyltransferase / Q000032:analysis / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology; D064429:Fatty Acid Synthases / Q000032:analysis / Q000378:metabolism*; D005910:Glioma / Q000201:enzymology*; D006801:Humans
chemical_list: D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases
keywords: acetyl-CoA carboxylase; carnitine palmitoyltransferase; fatty acid synthase; glioma; isocitrate dehydrogenase 1