Transcription factor AP-1 promotes growth and radioresistance in prostate cancer cells

  • Authors:
    • Risto Kajanne
    • Päivi Miettinen
    • Mikko Tenhunen
    • Sirpa Leppä
  • View Affiliations

  • Published online on: November 1, 2009     https://doi.org/10.3892/ijo_00000434
  • Pages: 1175-1182
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Abstract

Expression of AP-1 proteins has been associated with a more aggressive clinical outcome in prostate cancer. However, their role and regulation by upstream kinase pathways in response to ionizing radiation has remained elusive. Here, we show that constitutive AP-1 activity in prostate cancer cells is dependent on the activities of EGF-R and PI3K. While inhibition of EGF-R is associated with suppression of c-Jun expression and proliferation, inhibition of PI3K pathway suppresses expression of several AP-1 subunits and proliferation, and also sensitizes prostate cancer cells to γ-radiation. The importance of AP-1 as a mediator of proliferation and radiation responses is demonstrated by the findings that the expression of JunD, Fra-1 and Fra-2 siRNAs in prostate cancer cells suppress these cellular responses. Together, the findings show that AP-1 activity in prostate cancer cells mediates EGF-R and PI3K signalling, is essential for their proliferation, and confers protection against radiation-induced cell death. Thus, its inhibition would be a lucrative target for therapy in this widely increasing cancer type.

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November 2009
Volume 35 Issue 5

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

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Spandidos Publications style
Kajanne R, Miettinen P, Tenhunen M and Leppä S: Transcription factor AP-1 promotes growth and radioresistance in prostate cancer cells. Int J Oncol 35: 1175-1182, 2009
APA
Kajanne, R., Miettinen, P., Tenhunen, M., & Leppä, S. (2009). Transcription factor AP-1 promotes growth and radioresistance in prostate cancer cells. International Journal of Oncology, 35, 1175-1182. https://doi.org/10.3892/ijo_00000434
MLA
Kajanne, R., Miettinen, P., Tenhunen, M., Leppä, S."Transcription factor AP-1 promotes growth and radioresistance in prostate cancer cells". International Journal of Oncology 35.5 (2009): 1175-1182.
Chicago
Kajanne, R., Miettinen, P., Tenhunen, M., Leppä, S."Transcription factor AP-1 promotes growth and radioresistance in prostate cancer cells". International Journal of Oncology 35, no. 5 (2009): 1175-1182. https://doi.org/10.3892/ijo_00000434