Activation of a system A amino acid transporter, ATA1/SLC38A1, in human hepatocellular carcinoma and preneoplastic liver tissues.
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.
Kondoh
Nobuo
N
Department of Biochemistry, National Defense Medical College, Tokorozawa-shi, Saitama 359-8513, Japan. nkondoh@ndmc.ac.jp
Imazeki
Nobuo
N
Arai
Masaaki
M
Hada
Akiyuki
A
Hatsuse
Kazuo
K
Matsuo
Hirotaka
H
Matsubara
Osamu
O
Ohkura
Shuri
S
Yamamoto
Mikio
M
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
D026924:Amino Acid Transport System A; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C445761:SLC38A1 protein, human