Inhibition of NF-kappaB in fusogenic membrane glycoprotein causing HL-60 cell death: implications for acute myeloid leukemia.
Viral fusogenic membrane glycoproteins (FMGs) are new therapeutic genes for the control of tumor growth, the cellular mechanisms mediating cell death is non-apoptotic. However, the precise molecular mechanism remains to be elucidated. Here, we showed overexpression of HSP70 in HL-60 cells mediated by Gibbon Ape leukemia virus hyperfusogenic envelope protein (GALV-FMG) inhibited the nuclear translocation of p65, the transcriptive activity of NF-kappaB and prevented the degradation of IkappaB. NF-kappaB may negatively regulate HSP70 expression, which made a positive feed back loop for expression of HSP70. FMG expression in HL-60 cells leaded to the formation of multinucleated syncytia and cell death, the main death mode of cells is necrosis. This form of cell death should be effective in vivo, gene therapy basing on FMG deserve further study for the treatment of AML.
Tan
Li
L
State Key Laboratory, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China.
Jia
Hongyun
H
Liu
Ranyi
R
Wu
Jiangxue
J
Han
Hongyu
H
Zuo
Yufang
Y
Yang
Shiping
S
Huang
Wenlin
W
D016923:Cell Death; D002459:Cell Fusion; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D015726:Giant Cells / Q000378:metabolism; D018922:HL-60 Cells; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D017989:Leukemia Virus, Gibbon Ape / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000494:pharmacology; D016328:NF-kappa B / Q000494:pharmacology*; D010957:Plasmids / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation; D014760:Viral Fusion Proteins / Q000235:genetics
D018840:HSP70 Heat-Shock Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D014760:Viral Fusion Proteins