title: Activation of a system A amino acid transporter, ATA1/SLC38A1, in human hepatocellular carcinoma and preneoplastic liver tissues.
abstract: The expression of amino acid transporter (AT) mRNAs including A system (ATA1/SNAT1/SLC38A1, ATA2/SNAT2/SLC38A2 and ATA3/SNAT3/SLC38A4), L system (LAT1/SLC7A5 and LAT2/SLC7A8), and y+ (CAT2/SLC7A2) genes, were compared among hepatocellular carcinoma (HCC) and non-cancerous liver cells. Among them the ATA1 mRNA expression was significantly elevated in all HCC cell lines (HepG2, HLF, HuH7 and JHH4) examined compared with normal liver tissue. We further discovered that the expression of ATA1 mRNA was significantly activated in HCC tissues and also elevated in pre-malignant cirrhotic livers from HCC patients, compared with normal livers from non-HCC patients. The ATA1 protein was extensively accumulated in the cytoplasm of pre-malignant liver and most HCCs, while being weak or undetectably low in normal liver tissues. SiRNA-mediated suppression of endogenous ATA1 lowered the viability of HepG2 cells. Thus, the activation of ATA1 confers growth and survival advantages in pre-malignant and malignant liver lesions.
authors.affiliation: Department of Biochemistry, National Defense Medical College, Tokorozawa-shi, Saitama 359-8513, Japan. nkondoh@ndmc.ac.jp
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kondoh
authors.forename: Nobuo
authors.initials: N
authors.lastname: Imazeki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Arai
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Hada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hatsuse
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsubara
authors.forename: Shuri
authors.initials: S
authors.lastname: Ohkura
authors.forename: Mikio
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D026924:Amino Acid Transport System A / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D011230:Precancerous Conditions / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D015533:Transcriptional Activation
chemical_list: D026924:Amino Acid Transport System A; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C445761:SLC38A1 protein, human