Increased susceptibility to apoptosis in CD45(+) myeloma cells accompanied by the increased expression of VDAC1.
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.
Liu
S
S
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.
Ishikawa
H
H
Tsuyama
N
N
Li
F-J
FJ
Abroun
S
S
Otsuyama
K-I
KI
Zheng
X
X
Ma
Z
Z
Maki
Y
Y
Iqbal
M S
MS
Obata
M
M
Kawano
M M
MM
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*
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