title: Increased susceptibility to apoptosis in CD45(+) myeloma cells accompanied by the increased expression of VDAC1.
abstract: Expression of CD45 is quite variable in human myeloma cells and cell lines, such as U266, and CD45(+) U266 proliferates in response to a growth factor, interleukin-6. Here, we show that CD45(+) myeloma cell lines were more sensitive to various apoptotic stimuli, such as oxidative stress and endoplasmic reticulum (ER)-stress, than CD45(-) cells. Reactive oxygen species and calcium ion seemed to be involved in the susceptibility to apoptosis of CD45(+) U266. The activation of the src family kinases associated with CD45 phosphatase played an important role in the augmented apoptosis in CD45(+) U266 by oxidative stress. These results indicate that the CD45-expression renders myeloma cells competent for not only mitogenic but also apoptotic stimuli, resulting in either proliferation or apoptosis of CD45(+) myeloma cells dependently upon the circumstantial stimuli. Furthermore, voltage-dependent anion channel (VDAC) 1 was identified as a gene highly expressed in CD45(+) U266 by cDNA subtraction. The increased expression of VDAC1 seemed to augment the sensitivity to the ER-stress because the VDAC1-transfected U266 was more susceptible to the thapsigargin-induced apoptosis. Thus, CD45 expression accompanied by the increased VDAC1 expression sensitizes myeloma cells to the various extracellular stimuli that trigger apoptosis via the mitochondrial pathways.
authors.affiliation: Laboratory of Cellular Signal Analysis, Department of Bio-Signal Analysis, Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Ishikawa
authors.forename: N
authors.initials: N
authors.lastname: Tsuyama
authors.forename: F-J
authors.initials: FJ
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Abroun
authors.forename: K-I
authors.initials: KI
authors.lastname: Otsuyama
authors.forename: X
authors.initials: X
authors.lastname: Zheng
authors.forename: Z
authors.initials: Z
authors.lastname: Ma
authors.forename: Y
authors.initials: Y
authors.lastname: Maki
authors.forename: M S
authors.initials: MS
authors.lastname: Iqbal
authors.forename: M
authors.initials: M
authors.lastname: Obata
authors.forename: M M
authors.initials: MM
authors.lastname: Kawano
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D002118:Calcium / Q000502:physiology; D049109:Cell Proliferation; D017931:DNA Primers; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology*; D018384:Oxidative Stress; D051966:Phospholipase C gamma / Q000378:metabolism; D017382:Reactive Oxygen Species; D014407:Tumor Cells, Cultured; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics*
chemical_list: D017931:DNA Primers; D017382:Reactive Oxygen Species; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1; D017493:Leukocyte Common Antigens; D051966:Phospholipase C gamma; D002118:Calcium