Increased susceptibility to apoptosis in CD45(+) myeloma cells accompanied by the increased expression of VDAC1

Oncogene. 2006 Jan 19;25(3):419-29. doi: 10.1038/sj.onc.1208982.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Base Sequence
  • Calcium / physiology
  • Cell Proliferation
  • DNA Primers
  • Humans
  • Leukocyte Common Antigens / immunology*
  • Multiple Myeloma / immunology*
  • Oxidative Stress
  • Phospholipase C gamma / metabolism
  • Reactive Oxygen Species
  • Tumor Cells, Cultured
  • Voltage-Dependent Anion Channel 1 / genetics*


  • DNA Primers
  • Reactive Oxygen Species
  • VDAC1 protein, human
  • Voltage-Dependent Anion Channel 1
  • Leukocyte Common Antigens
  • Phospholipase C gamma
  • Calcium