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

Oncogene volume 25, pages 419–429 (2006)Cite this article

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.

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References

  • Abe J and Berk BC . (1999). J. Biol. Chem., 274, 21003–21010.

  • Abe J, Okuda M, Huang Q, Yoshizumi M and Berk BC . (2000). J. Biol. Chem., 275, 1739–1748.

  • Abe J, Takahashi M, Ishida M, Lee JD and Berk BC . (1997). J. Biol. Chem., 272, 20389–20394.

  • Abroun S, Ishikawa H, Tsuyama N, Liu S, Li FJ, Otsuyama K, Zheng X, Obata M and Kawano MM . (2004). Blood, 103, 2291–2298.

  • Adams JM and Cory S . (1998). Science, 281, 1322–1326.

  • Antonsson B and Martinou JC . (2000). Exp. Cell Res., 256, 50–57.

  • Bernardi P . (1999). Physiol. Rev., 79, 1127–1155.

  • Cahir McFarland ED, Hurley TR, Pingel JT, Sefton BM, Shaw A and Thomas ML . (1993). Proc. Natl. Acad. Sci. USA, 90, 1402–1406.

  • Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinski L, Fernandez-Luna JL, Nunez G, Dalton WS and Jove R . (1999). Immunity, 10, 105–115.

  • Charbonneau H and Tonks NK . (1992). Annu. Rev. Cell Biol., 8, 463–493.

  • Corey SJ and Anderson SM . (1999). Blood, 93, 1–14.

  • Decaudin D, Geley S, Hirsch T, Castedo M, Marchetti P, Macho A, Kofler R and Kroemer G . (1997). Cancer Res., 57, 62–67.

  • Devary Y, Gottlieb RA, Smeal T and Karin M . (1992). Cell, 71, 1081–1091.

  • Ferri KF and Kroemer G . (2001). Nat. Cell Biol., 3, E255–E263.

  • Fujii R, Ishikawa H, Mahmoud MS, Asaoku H and Kawano MM . (1999). Br. J. Haematol., 105, 131–140.

  • Ishikawa H, Tsuyama N, Abroun S, Liu S, Li FJ, Taniguchi O and Kawano MM . (2002). Blood, 99, 2172–2178.

  • Joshua D, Petersen A, Brown R, Pope B, Snowdon L and Gibson J . (1996). Br. J. Haematol., 94, 76–81.

  • Justement LB . (2001). Int. Rev. Immunol., 20, 713–738.

  • Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, Kuramoto A and Kishimoto T . (1988). Nature, 332, 83–85.

  • Kawano MM, Huang N, Harada H, Harada Y, Sakai A, Tanaka H, Iwato K and Kuramoto A . (1993). Blood, 82, 564–570.

  • Kawano MM, Mihara K, Huang N, Tsujimoto T and Kuramoto A . (1995). Blood, 85, 487–494.

  • Korsmeyer SJ . (1999). Cancer Res., 59, 1693–1700.

  • Kroemer G and Reed JC . (2000). Nat. Med., 6, 513–519.

  • Li F-J, Tsuyama N, Ishikawa H, Obata M, Abroun S, Liu S, Otsuyama K-I, Zheng X, Ma Z, Maki Y and Kawano MM . (2005). A rapid translocation of CD45RO but not CD45RA to lipid rafts in IL-6-induced proliferation in myeloma. Blood, 105, 3295–3302.

    Article  CAS  Google Scholar 

  • Lipton SA and Nicotera P . (1998). Cell Calcium, 23, 165–171.

  • Loeffler M and Kroemer G . (2000). Exp. Cell Res., 256, 19–26.

  • Mahmoud MS, Ishikawa H, Fujii R and Kawano MM . (1998). Blood, 92, 3887–3897.

  • Mazzoni A, Young HA, Spitzer JH, Visintin A and Segal DM . (2001). J. Clin. Invest., 108, 1865–1873.

  • Mustelin T and Altman A . (1990). Oncogene, 5, 809–813.

  • Mustelin T, Coggeshall KM and Altman A . (1989). Proc. Natl. Acad. Sci. USA, 86, 6302–6306.

  • Namba M, Ohtsuki T, Mori M, Togawa A, Wada H, Sugihara T, Yawata Y and Kimoto T . (1989). In vitro Cell Dev. Biol., 25, 723–729.

  • Ostergaard HL and Trowbridge IS . (1990). J. Exp. Med., 172, 347–350.

  • Ostergaard HL, Shackelford DA, Hurley TR, Johnson P, Hyman R, Sefton BM and Trowbridge IS . (1989). Proc. Natl. Acad. Sci. USA, 86, 8959–8963.

  • Rampino N, Yamamoto H, Ionov Y, Li Y, Sawai H, Reed JC and Perucho M . (1997). Science, 275, 967–969.

  • Rapizzi E, Pinton P, Szabadkai G, Wieckowski MR, Vandecasteele G, Baird G, Tuft RA, Fogarty KE and Rizzuto R . (2002). J. Cell Biol., 159, 613–624.

  • Rizzuto R, Simpson AW, Brini M and Pozzan T . (1992). Nature, 358, 325–327.

  • Schneider U, van Lessen A, Huhn D and Serke S . (1997). Br. J. Haematol., 97, 56–64.

  • Shimizu S, Matsuoka Y, Shinohara Y, Yoneda Y and Tsujimoto Y . (2001). J. Cell Biol., 152, 237–250.

  • Shimizu S, Narita M and Tsujimoto Y . (1999). Nature, 399, 483–487.

  • Shimizu S, Takiguchi T, Fukutoku M, Yoshioka R, Hirose Y, Fukuhara S, Ohno H, Isobe Y and Konda S . (1993). Leukemia, 7, 274–280.

  • Takagi-Morishita Y, Yamada N, Sugihara A, Iwasaki T, Tsujimura T and Terada N . (2003). Biol. Reprod., 68, 1178–1184.

  • Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF and Reed JC . (1999). Science, 284, 339–343.

  • Yoshizumi M, Abe J, Haendeler J, Huang Q and Berk BC . (2000). J. Biol. Chem., 275, 11706–11712.

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Acknowledgements

We thank Dr Harumi Suzuki (Yamaguchi University) and Dr Hideki Asaoku (Hiroshima Red Cross Hospital) for providing us a retrovirus vector, pMx-puro and bone marrow aspirates from myeloma patients, respectively. We also thank the Center for Gene Research, Yamaguchi University for DNA sequencing. This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture of Japan, the Ministry of Health, Labour and Welfare of Japan, the Japan Society for the Promotion of Science (JSPS), Mitsubishi Pharma Research Foundation and International Myeloma Foundation. JSPS Postdoctoral Fellowship for Foreign Researchers (P04500) awarded to SA.

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  1. Department of Bio-Signal Analysis, Laboratory of Cellular Signal Analysis, Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, 755-8505, Yamaguchi, Japan

    S Liu, H Ishikawa, N Tsuyama, F-J Li, S Abroun, K-i Otsuyama, X Zheng, Z Ma, Y Maki, M S Iqbal, M Obata & M M Kawano

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  1. S Liu
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  2. H Ishikawa
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Correspondence to H Ishikawa.

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Liu, S., Ishikawa, H., Tsuyama, N. et al. Increased susceptibility to apoptosis in CD45+ myeloma cells accompanied by the increased expression of VDAC1. Oncogene 25, 419–429 (2006). https://doi.org/10.1038/sj.onc.1208982

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