Modulation of Janus kinase 2 by cisplatin in cancer cells

  • Authors:
    • Hui Song
    • Vernon K. Sondak
    • Dwayne L. Barber
    • Thomas J. Reid
    • Jiayuh Lin
  • View Affiliations

  • Published online on: April 1, 2004     https://doi.org/10.3892/ijo.24.4.1017
  • Pages: 1017-1026
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Abstract

Constitutive activation of Janus kinases (JAKs) is frequently detected in various human cancers. The activation of JAKs results in the phosphorylation and activation of signal transducers and activators of transcription (STATs). The constitutive activation of JAK/STAT pathway may play an important role in growth and survival of human cancer cells. In this study, we examined whether a chemotherapeutic agent cisplatin could inhibit the JAK/STAT pathway. In ovarian cancer and sarcoma cells that express constitutively active JAK2, cisplatin significantly inhibited tyrosine phosphorylation and kinase activity of JAK2 in a dose- and time-dependent manner. Meanwhile, cisplatin also inhibited Stat3 tyrosine phosphorylation and down-regulated BcL-XL anti-apoptotic protein in the cancer cells tested. In leukemia cells expressing high level of TEL-JAK2 fusion protein, cisplatin dramatically inhibited tyrosine phosphorylation of TEL-JAK2 as well. Furthermore, our results have shown that down-regulation of JAK2 by cisplatin might be through modulation of a tyrosine phosphatase SHP-1 but not SOCS family members. Taken together, our observations demonstrated that cisplatin down-regulated the JAK/STAT pathway through de-phosphorylation of JAK/STAT in cancer cells.

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April 2004
Volume 24 Issue 4

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

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APA
Song, H., Sondak, V.K., Barber, D.L., Reid, T.J., & Lin, J. (2004). Modulation of Janus kinase 2 by cisplatin in cancer cells. International Journal of Oncology, 24, 1017-1026. https://doi.org/10.3892/ijo.24.4.1017
MLA
Song, H., Sondak, V. K., Barber, D. L., Reid, T. J., Lin, J."Modulation of Janus kinase 2 by cisplatin in cancer cells". International Journal of Oncology 24.4 (2004): 1017-1026.
Chicago
Song, H., Sondak, V. K., Barber, D. L., Reid, T. J., Lin, J."Modulation of Janus kinase 2 by cisplatin in cancer cells". International Journal of Oncology 24, no. 4 (2004): 1017-1026. https://doi.org/10.3892/ijo.24.4.1017