Cellular localization and functional characterization of the equilibrative nucleoside transporters of antitumor nucleosides.
Nucleoside transporters play an important role in the disposition of nucleosides and their analogs. To elucidate the relationship between chemosensitivity to antitumor nucleosides and the functional expression of equilibrative nucleoside transporters (ENT), we established stable cell lines of human fibrosarcoma HT-1080 and gastric carcinoma TMK-1 that constitutively overexpressed green fluorescent protein-tagged hENT1, hENT2, hENT3 and hENT4. Both hENT1 and hENT2 were predictably localized to the plasma membrane, whereas hENT3 and hENT4 were localized to the intracellular organelles. The chemosensitivity of TMK-1 cells expressing hENT1 and hENT2 to cytarabine and 1-(3-C-ethynyl-beta-D-ribopentofuranosyl) cytosine increased markedly in comparison to that of mock cells. However, no remarkable changes in sensitivity to antitumor nucleosides were observed in cell lines that expressed both hENT3 and hENT4. These data suggest that hENT3 and hENT4, which are mainly located in the intracellular organelles, are not prominent nucleoside transporters like hENT1 and hENT2, which are responsible for antitumor nucleoside uptake.
Endo
Yoshio
Y
Department of Experimental Therapeutics, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan. yendo@kenroku.kanazawa-u.ac.jp
Obata
Tohru
T
Murata
Daigo
D
Ito
Mariho
M
Sakamoto
Kazuki
K
Fukushima
Masakazu
M
Yamasaki
Yasundo
Y
Yamada
Yuji
Y
Natsume
Nagato
N
Sasaki
Takuma
T
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D003561:Cytarabine / Q000494:pharmacology*; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D033705:Equilibrative Nucleoside Transport Proteins / Q000235:genetics / Q000378:metabolism; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics / Q000378:metabolism; D033722:Equilibrative-Nucleoside Transporter 2 / Q000235:genetics / Q000378:metabolism; D005354:Fibrosarcoma / Q000188:drug therapy / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D033703:Nucleoside Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
C103084:1-(3-C-ethynylribopentofuranosyl)cytosine; D000964:Antimetabolites, Antineoplastic; D033705:Equilibrative Nucleoside Transport Proteins; D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2; D033703:Nucleoside Transport Proteins; D012333:RNA, Messenger; C438649:SLC29A1 protein, human; C438654:SLC29A2 protein, human; C501424:SLC29A3 protein, human; C495988:SLC29A4 protein, human; C485184:enhanced green fluorescent protein; D003561:Cytarabine; D049452:Green Fluorescent Proteins; D003562:Cytidine
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