Modulation of Raf/MEK/ERK kinase activity does not affect the chemoresistance profile of advanced prostate cancer cells

  • Authors:
    • John T. Lee
    • Linda S. Steelman
    • James A. McCubrey
  • View Affiliations

  • Published online on: June 1, 2005     https://doi.org/10.3892/ijo.26.6.1637
  • Pages: 1637-1644
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The Raf/MEK/ERK signaling cascade has been extensively studied for its roles in growth and differentiation of a variety of cell types. Confliciting evidence exists regarding the function of classical MAPK signaling with regards to the development of chemotherapeutic drug resistance; some reports describe an pro-survival role, whereas others have suggested that activation of Raf/MEK/ERK is essential for drug-induced death. To elucidate the importance of MAPK signaling in the development of advanced prostate cancer drug resistance, DU145 and PC3 prostate cells were stably-infected/transfected with constitutively-activated mutants of both Raf-1 and B-Raf. Results from MTT analyses suggested that activation of either Raf-1 or B-Raf is inconsequential in prostate cancer chemoresistance. To confirm these findings, the MAPK signal transduction cascade was activated with EGF and response to doxorubicin or paclitaxel was measured in the presence/absence of the MEK-specific inhibitor, U0126. These results showed that inhibition of signals transduced by the MAPK pathway are insufficient to affect the chemoresistance profile of advanced prostate cancer cells. Together, these data demonstrate that the response of prostatic tumors to the chemotherapeutic compounds doxorubicin and paclitaxel is independent of Raf/MEK/ERK signaling.

Related Articles

Journal Cover

June 2005
Volume 26 Issue 6

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Lee JT, Steelman LS and McCubrey JA: Modulation of Raf/MEK/ERK kinase activity does not affect the chemoresistance profile of advanced prostate cancer cells. Int J Oncol 26: 1637-1644, 2005
APA
Lee, J.T., Steelman, L.S., & McCubrey, J.A. (2005). Modulation of Raf/MEK/ERK kinase activity does not affect the chemoresistance profile of advanced prostate cancer cells. International Journal of Oncology, 26, 1637-1644. https://doi.org/10.3892/ijo.26.6.1637
MLA
Lee, J. T., Steelman, L. S., McCubrey, J. A."Modulation of Raf/MEK/ERK kinase activity does not affect the chemoresistance profile of advanced prostate cancer cells". International Journal of Oncology 26.6 (2005): 1637-1644.
Chicago
Lee, J. T., Steelman, L. S., McCubrey, J. A."Modulation of Raf/MEK/ERK kinase activity does not affect the chemoresistance profile of advanced prostate cancer cells". International Journal of Oncology 26, no. 6 (2005): 1637-1644. https://doi.org/10.3892/ijo.26.6.1637