Abstract A78: Role of PTEN and ionizing radiation in underpinning differential activation of interleukin‐8 in prostate cancer cells

Prostate cancer (CaP) cells exhibit varying sensitivity to radiotherapy. Previous studies of our group showed that the synthesis of the CXC‐chemokine Interleukin‐8 (CXCL8) is linked to resistance of cancer cells to environmental and chemical stresses. Accordingly, we wished to explore the impact of ionizing radiation in modulating Interleukin‐8 expression in Prostate Cancer cells (PC) in vitro . IR (3Gy) induced rapid time‐dependent, NFiB transcriptional activity in PC3 and LNCaP cells that co‐incided with the detection of increased mRNA transcript levels for CXCL8 in both cell lines. However, although a same rapid increase in IL‐8 mRNA was observed in Du145 and 22Rv1 cells, they show a more pronounced AP‐1 activation, suggesting that in this prostate cancer cell lines signalling cascade to IL‐8 mRNA synthesis is mainly driven by AP‐1. Immunoblotting also confirmed that expression of CXCL8 increased rapidly in PC3 and LNCaP cells in response to IR (30 min to 2 hours). Subsequently, we investigated the importance of the tumor suppressor gene Phosphate and Tensin Homolog (PTEN) in underpinning this differential response of PC3 and LNCaP (PTEN‐null) compared to Du145 and 22Rv1 (PTEN‐wt) cells to IR. Moreover we sought to clarify the link between the PTEN‐status in our in vitro model and the activation of PI3K, MAPKs and PKC pro‐survival pathways after exposure of cells to Ionizing Radiation. Accordingly, we will continue to explore our hypothesis that PTEN acts as a master regulator of radiosensitivity in CaP cells by activating signal transduction pathways in irradiated cells. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A78.