title: Reduction of transforming growth factor-β1 expression in leukemia and its possible role in leukemia development.
abstract: The expression of transforming growth factor-β1 (TGF-β1) in leukemic cells and sera from patients with leukemia and its possible role in leukemia development were studied. TGF-β1 levels in culture supernatants from leukemic cells were significantly lower than those from normal bone marrow mononuclear cells. Serum TGF-β1 levels in leukemic patients were significantly lower compared with healthy controls, but returned to normal in patients achieving complete remission, and decreased when patients relapsed. TGF-β1 mRNA expression levels were significantly higher in normal bone marrow mononuclear cells but lower in leukemic cells compared with normal CD34 + cells. After transfection of the TGF-β1 gene to HL-60 cells, cell apoptosis was detected. Moreover, by flow cytometry analysis, cells arrested in G1 phase were 62% for TGF-β1 transfected cells and 44% for controls. Transfection of exogenous TGF-β1 gene inhibited HL60 cells xenograft growth in nude mice, and prolonged survival of tumor-bearing mice compared with the controls. Decreased endogenous TGF-β1 expression in leukemia cells may be involved in leukemia development, Transfection of exogenous TGF-B1 gene to HL60 can inhibit the proliferation of the cells and induce cell apoptosis by down regulating bcl-2, hTERT (human telomerase reverse transcriptase) and c-myc expression.
authors: Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
authors: Yong
authors: Y
authors: Wu
authors: Ping
authors: P
authors: Chen
authors: Hui-Fang
authors: HF
authors: Huang
authors: Mei-Juan
authors: MJ
authors: Huang
authors: Yuan-Zhong
authors: YZ
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D016193:G1 Phase / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D015316:Genetic Therapy / Q000379:methods*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D053773:Transforming Growth Factor beta1; C509186:TERT protein, human; D019098:Telomerase