       Document 0940
 DOCN  M9620940
 TI    Constitutive overexpression of the L-selectin gene in fresh leukemic
       cells of adult T-cell leukemia that can be transactivated by human
       T-cell lymphotropic virus type 1 Tax.
 DT    9602
 AU    Tatewaki M; Yamaguchi K; Matsuoka M; Ishii T; Miyasaka M; Mori S;
       Takatsuki K; Watanabe T; Department of Pathology, University of Tokyo,
       Japan.
 SO    Blood. 1995 Oct 15;86(8):3109-17. Unique Identifier : AIDSLINE
       MED/96017245
 AB    L-selectin is an adhesion molecule of the selectin family that mediates
       the initial step of leukocyte adhesion to vascular endothelium. Upon
       cellular activation, expression of the L-selectin gene is downregulated
       at both the protein and mRNA levels. To understand the mechanism of
       leukemic cell infiltration into organs, we studied the expression and
       regulation of L-selectin mRNA in fresh leukemic cells of adult T-cell
       leukemia (ATL) patients and investigated the response of the L-selectin
       promoter to human T-cell lymphotropic virus type 1 (HTLV-1) Tax, which
       is a viral transcriptional transactivator. Flow cytometry showed that
       L-selectin was expressed on fresh ATL cells along with other activation
       antigens. Northern blot analysis showed that ATL cells overexpressed
       that L-selectin mRNA and that the level was aberrantly upregulated after
       PMA stimulation. Studies using in situ hybridization showed expression
       of the L-selectin mRNA in the infiltrating leukemic cells in the liver
       of two ATL patients. Intravenous injection of a rat T-cell line that
       overexpresses L-selectin showed increased organ infiltration. The
       induction of Tax expression in JPX9 cells resulted in about a twofold
       increase in the mRNA expression levels compared with the basal level.
       Chloramphenicol acetyltransferase (CAT) assay after transient
       cotransfection showed about a fivefold transactivation of the L-selectin
       promoter by Tax. The serum level of the shed form of L-selectin was
       significantly increased in ATL patients (mean +/- SD, 4,215.4 +/- 4,111
       ng/mL) compared with those of asymptomatic carriers and healthy blood
       donors (mean +/- SD, 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL,
       respectively). These results indicated that ATL cells constitutively
       overexpress the L-selectin gene that can be transactivated by HTLV-1
       Tax. The overexpression of L-selectin, as well as of inflammatory
       cytokines, by ATL cells may provide a basis for ATL cells to attach the
       vascular endothelium, leading to transmigration and organ infitration.
 DE    Adult  Animal  Carrier State  Cell Adhesion  Gene Expression Regulation,
       Leukemic/*DRUG EFFECTS  Gene Products, tax/*PHARMACOLOGY  Human
       HTLV-I/GENETICS/*PHYSIOLOGY
       L-Selectin/*BIOSYNTHESIS/GENETICS/PHYSIOLOGY  Leukemia-Lymphoma, T-Cell,
       Acute, HTLV-I-Associated/GENETICS/  *PATHOLOGY  Leukemic
       Infiltration/*PHYSIOPATHOLOGY  Liver/PATHOLOGY  Neoplasm
       Proteins/*BIOSYNTHESIS/GENETICS/PHYSIOLOGY  Promoter Regions (Genetics)
       Rats  Recombinant Fusion Proteins/BIOSYNTHESIS  Repetitive Sequences,
       Nucleic Acid  RNA, Messenger/BIOSYNTHESIS  RNA, Neoplasm/BIOSYNTHESIS
       Support, Non-U.S. Gov't  T-Lymphocytes/TRANSPLANTATION
       Tetradecanoylphorbol Acetate/PHARMACOLOGY  *Trans-Activation (Genetics)
       Transcription Factors/PHYSIOLOGY  Tumor Stem Cells/DRUG
       EFFECTS/*METABOLISM  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

