Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 35, Issue 5, Pages 1175-1182Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo_00000434
Keywords
AP-1; EGF-R; AKT; growth; radiation; prostate cancer
Categories
Funding
- Finnish Academy of Sciences
- Finnish Cancer Societies
- Sigrid Juselius, Paolo, and K. Albin Johansson (R.K.) Foundations
- University of Helsinki
- Helsinki University Central Hospital
- AstraZeneca
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available