Ectopic cyclin D1 overexpression increases chemosensitivity but not cell proliferation in multiple myeloma

  • Authors:
    • Yoshiaki Kuroda
    • Akira Sakai
    • Naohiro Tsuyama
    • Yuta Katayama
    • Shoso Munemasa
    • Hideki Asaoku
    • Yoshiko Okikawa
    • Nanae Nakaju
    • Mami Mizuno
    • Katsunari Ogawa
    • Takashi Nishisaka
    • Hirotaka Matsui
    • Hideo Tanaka
    • Akiro Kimura
  • View Affiliations

  • Published online on: December 1, 2008     https://doi.org/10.3892/ijo_00000110
  • Pages: 1201-1213
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Abstract

We established a myeloma cell line (RPMI8226) with cyclin D1 overexpression in which the transfected cyclin D1 gene was stably expressed. D1 transfectants showed down-regulation of cyclin D2. Cell proliferation analysis did not show any differences among RPMI8226, mock control, and D1 transfectants. The number of S-phase cells increased while the number of G0/G1- and G2/M-phase cells decreased in D1 transfectants, which indicates a prolonged S-phase caused by cyclin D1 transfection. A decreased number of G2/M-phase cells was also detected in myeloma cells of patients with translocation t(11;14)(q13;q32). Western blot analysis revealed an increase in the hyperphosphorylated form of retinoblastoma (Rb) protein in D1 transfectants; however, the expression of p53, p16, Bax, Bad, Bcl-2, and Mcl-1 did not significantly change. Treatment with anti-myeloma drugs (melphalan, dexamethasone, bortezomib and immunomodulatory compounds) induced apoptosis earlier in D1 transfectants compared with RPMI8226 and mock control via the activation of both caspase-8 and -9. However, we could not detect a relationship between cyclin D1 expression and the response to treatment with VAD and bortezomib. Therefore, we assume that high sensitivity to anti-myeloma drugs depends on the duration of the S-phase, but a clinical response might depend on the number of myeloma cells with cyclin D1 overexpression.

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December 2008
Volume 33 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kuroda Y, Sakai A, Tsuyama N, Katayama Y, Munemasa S, Asaoku H, Okikawa Y, Nakaju N, Mizuno M, Ogawa K, Ogawa K, et al: Ectopic cyclin D1 overexpression increases chemosensitivity but not cell proliferation in multiple myeloma. Int J Oncol 33: 1201-1213, 2008.
APA
Kuroda, Y., Sakai, A., Tsuyama, N., Katayama, Y., Munemasa, S., Asaoku, H. ... Kimura, A. (2008). Ectopic cyclin D1 overexpression increases chemosensitivity but not cell proliferation in multiple myeloma. International Journal of Oncology, 33, 1201-1213. https://doi.org/10.3892/ijo_00000110
MLA
Kuroda, Y., Sakai, A., Tsuyama, N., Katayama, Y., Munemasa, S., Asaoku, H., Okikawa, Y., Nakaju, N., Mizuno, M., Ogawa, K., Nishisaka, T., Matsui, H., Tanaka, H., Kimura, A."Ectopic cyclin D1 overexpression increases chemosensitivity but not cell proliferation in multiple myeloma". International Journal of Oncology 33.6 (2008): 1201-1213.
Chicago
Kuroda, Y., Sakai, A., Tsuyama, N., Katayama, Y., Munemasa, S., Asaoku, H., Okikawa, Y., Nakaju, N., Mizuno, M., Ogawa, K., Nishisaka, T., Matsui, H., Tanaka, H., Kimura, A."Ectopic cyclin D1 overexpression increases chemosensitivity but not cell proliferation in multiple myeloma". International Journal of Oncology 33, no. 6 (2008): 1201-1213. https://doi.org/10.3892/ijo_00000110