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

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 gamma-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.

• Authors: Risto Kajanne, Päivi Miettinen, Mikko Tenhunen, Sirpa Leppä
• Journal: International journal of oncology (Int J Oncol) Vol. 35 Issue 5 Pg. 1175-82 (Nov 2009) ISSN: 1791-2423 [Electronic] Greece
• PMID: 19787273 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Transcription Factor AP-1
• Phosphatidylinositol 3-Kinases
• ErbB Receptors

Topics

• Apoptosis (genetics, radiation effects)
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation (radiation effects)
• Electrophoretic Mobility Shift Assay
• ErbB Receptors (genetics, metabolism)
• Humans
• Male
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Prostatic Neoplasms (genetics, metabolism, pathology)
• Radiation Tolerance (genetics)
• Signal Transduction (genetics, radiation effects)
• Transcription Factor AP-1 (genetics, metabolism)