title: Suppression of amino acid transporter LAT3 expression on proliferation of K562 cells.
abstract: The activity of the mTOR pathway is frequently increased in acute myeloid leukemia, and is tightly related with cellular proliferation. Leucine is tightly linked to the mTOR pathway and can activate it, thereby stimulating cellular proliferation. LAT3 is a major transporter for leucine, and suppression of its expression can reduce cell proliferation. Here, we show that suppression of LAT3 expression can reduce proliferation of the acute leukemia cell line, K562. We investigated the mRNA and protein expression of LAT3 in several leukemia cell lines and normal peripheral blood mononuclear cells (PBMNCs) using RT-PCR and Western blotting. We also evaluated cell viability using a methyl thiazolyl tetrazolium (MTT) assay after blocking LAT3 expression with either shRNA targeted to LAT3 or a small molecular inhibitor BCH (2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid). LAT3 mRNA and protein expression was detected in leukemia cell lines, but not in normal PBMNCs. Using K562 cells, it was found that cellular proliferation and mTOR pathway activity were significantly reduced when LAT3 was blocked with either shRNA or BCH. Our results suggest that leukemia cell proliferation can be significantly suppressed by blocking LAT3. This finding may lead to a new strategy to develop clinical therapy for the treatment of acute myeloid leukemia.
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Si-Miao
authors.initials: SM
authors.lastname: Xu
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tang
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Li
authors.initials: L
authors.lastname: Meng
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. tangyi_100@tom.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000598:Amino Acids, Cyclic / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D026923:Amino Acid Transport Systems, Basic; D000598:Amino Acids, Cyclic; C469951:SLC7A6 protein, human; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D058570:TOR Serine-Threonine Kinases