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Altered Nuclear Localization of Bax Protein in BCNU-resistant Glioma Cells

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Abstract

To investigate the role of apoptosis suppression in glioma chemotherapy resistance, protein levels and subcellular localization of bcl-2 family members were investigated in 2 pairs of sensitive cell lines and their in vitro generated resistant derivatives. The alkylating agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), induced apoptosis in both sensitive cell strains and apoptosis was suppressed in both resistant derivatives. Both resistant cell lines contained altered regulation of a bcl-2 related protein consistent with the suppression of apoptosis. Independent of which bcl-2 family member was dysregulated, resistance was associated with altered regulation in the subcellular localization of bax protein. Following BCNU treatment, bax accumulated in nucleoli and a nuclei containing fraction of sensitive cells but not their resistant derivatives. Nuclear accumulation was an early event in apotosis induction. These data indicates altered subcellular localization of bax may play a role in resistance. In addition, the association between an early, nucleolar localization of bax and the induction of apoptosis suggests that localization of bax to nucleoli may play a role in apoptosis-induction of glioma cells.

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References

  1. Bobola MS, Berger MS, Silber JR: Mol Carc, 13: 81-5, 1995

    Google Scholar 

  2. Saito Y, Nakada Y, Hotta T, Mikami T, Kurisu K, Yamada K, Kiya K, Kawamoto K, Uozimi T: T Internat J Can 48: 861-5, 1997

    Google Scholar 

  3. Nunez G, Clarke MF: Trends Cell Biol 4: 399-403, 1994

    Google Scholar 

  4. Reed JC: Oncol Hematol 9: 451-71, 1995

    Google Scholar 

  5. Campos L, Roualuit J, Sabido O, Roubi N, Vasselon C, Archimbaud E, Magaud J, Guyotat D: Blood 81: 3091-6, 1993

    Google Scholar 

  6. McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LWK, Hsieh J, Tu S, Campbell ML: Cancer Res 52: 6940-4, 1992

    Google Scholar 

  7. Bargou RC, Daniel PT, Mapara MY, Bommert K, Wagener C, Kallinich BR, Dorken HD: Inter J Can 60: 854-9, 1995

    Google Scholar 

  8. Joy A, Shapiro JR: Proc Amer Assoc Cancer Res Special Conference on Programmed Cell Death 1: B17, 1996

    Google Scholar 

  9. Oltvai ZN, Milliman CL, Korsmeyer SJ: Cell 74: 609-19, 1993

    Google Scholar 

  10. Xiang J, Chao DT, Korsmeyer SJ: Proc Natl Acad Sci USA 93: 14 559-63, 1996

    Google Scholar 

  11. Wolter KG, Hsu Y, Smith CL, Nechushtan A, Xi X, Youle RJ: J Cell Biol 139: 1281-92, 1997

    Google Scholar 

  12. Krajewski S, Krajewski M, Shabaik A, Miyashita T, Wang HG, Reed JC: Amer J Path 145: 1323-9, 1994

    Google Scholar 

  13. Han J, Sabbatini P, Perez D, Rao L, Modha D, White E: Genes & Dev 461-77, 1995

  14. Gross A, Jockel J, Wei MC, Korsmeyer SJ: EMBO J 17: 3878-85, 1998

    Google Scholar 

  15. Quignon F, De Bels F, Koken M, Feunteun J, Ameisen J, de The H: Nature Genet 20: 259-65, 1998

    Google Scholar 

  16. Hsu YT, Wolter KG, Youle RJ: Proc Natl Acad Sci USA 94: 3668-72, 1997

    Google Scholar 

  17. Mandal M, Adam L, Mendelsohn J, Kumar R: Oncogene 17: 999-1007, 1998

    Google Scholar 

  18. Rogalsky V, Todorov G, Moran D: Biochem Biophys Res Commun 192: 1139-46, 1993

    Google Scholar 

  19. Borden KL, Campbelldwyer EJ, Carlile GW, Djavani M, Salvato MS: Mol Brain Res 38: 161-5, 1998

    Google Scholar 

  20. Desbois C, Rousset R, Bantignies F, Jalinot P: Science 273: 951-3, 1996

    Google Scholar 

  21. Desnoyers S, Kaufman SH, Poirier GG: Alteration of the nucleolar localization of poly(ADP-ribose) polymerase upon treatment with transcription inhibitors. Exp Cell Res 227(1): 146-53, 1996

    Google Scholar 

  22. Bouche G, Gas N, Prats H, Baldin V, Tauber JP, Teissie JAF: Proc Natl Acad Sci USA 84: 6770-4, 1997

    Google Scholar 

  23. Hattori H, Kaneda T, Lokeshwar B, Laszlo A, Ohtsuka K: Cell Science 104: 629-38, 1993

    Google Scholar 

  24. Fukamachi AT, Kanazawa Y, Furukawa H, Shimizu K, Hirana T, Kasai H, Kashimura M, Higashi K: Jap J Can Res 87: 945-51, 1996

    Google Scholar 

  25. Henderson JE, Amizuka N, Warshawsky H, Biasotto D, Lanske BM, Goltzman D, Karaplis AC: Mol Cell Biol 15: 4064-75, 1995

    Google Scholar 

  26. Shapiro JR, Yung WA, Shapiro WR: Can Res 41: 2349-59, 1981

    Google Scholar 

  27. Schwartz LM, Osborne BA: Cell death. Academic Press, San Diego, 1995, p 172-173

    Google Scholar 

  28. Joy A, Moffett J, Neary K, Mordechai E, Stachowiak EK, Coons S, Rankin-Shapiro J, Florkiewicz RZ, Stachowiak MK: Oncogene 14: 171-83, 1997

    Google Scholar 

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Authors and Affiliations

  1. Laboratory of Neuro-Oncology, Barrow Neurological Institute, Phoenix, AZ, USA

    A. Joy, S. Panicker & J.R. Shapiro

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  1. A. Joy
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  2. S. Panicker
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  3. J.R. Shapiro
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Joy, A., Panicker, S. & Shapiro, J. Altered Nuclear Localization of Bax Protein in BCNU-resistant Glioma Cells. J Neurooncol 49, 117–129 (2000). https://doi.org/10.1023/A:1026574123273

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