Cell and Tissue Signaling
Tuesday, October 18, 2005 3:00 PM-5:00 PM Exhibit Hall(PP272) Insulin-like growth factor type I receptor (IGF-IR) mediates radioresistance of DU-145 and PC3 human prostate cancer cells during ionizing radiation.
Wang, Tao *,1, 2, 4, Languino, Lucia2, 3, 4, FitzGerald, Thomas1, 4, 1 Radiation Oncology, Worcester, MA, USA2 Cancer Biology, Worcester, MA, USA4 Cancer Center, Worcester, MA, USA3 Cell Biology, Worcester, MA, USA
ABSTRACT- Introduction/Objectives: Although IGF is a potent survival factor for both normal and malignant prostate epithelial cells, the role of IGF-IR in mediating radioresistance of prostate cancer cells is poorly understood. In this study, we investigated the expression of IGF-IR and the role of IGF-IR in cell survival in two androgen-independent prostate cancer cells, DU-145 and PC3, exposed to ionizing radiation. Materials and Methods: DU-145 and PC3 cells were irradiated at room temperature with x-rays. After radiation, cells were collected and analyzed using immunoblotting (IB) and FACS analysis to determine the expression of IGF-IR. Cell survival was determined using clonogenic assays after cells were stimulated with IGF-I. Activation of IGF-IR was detected using immunoprecipitation (IP) and immunoblot analysis. Results: DU-145 cells expressed IGF-IR at a higher level than PC3 cells and showed a higher radioresistance (one log difference) in clonogenic assays. When stimulated with 50 ng/ml IGF, both cell lines showed a statistically significant difference of radioresistance as compared to non-treated cells. Late-passage PC3 cells that failed to express IGF-IR showed no difference in radioresistance in the presence or absence of IGF-I. Furthermore, IGF-IR null cells stably transfected with IGF-IR (R+) showed a much stronger radioresistance than control cells (R-) that lack IGF-IR expression. Finally, IGF-IR was activated in DU-145 cells exposed to 25 Gy but not to 5 Gy as determined with an antibody specific to phosphorylated proteins in IP and IB analysis. Conclusions: Our data suggest that IGF-IR plays a critical role in mediating cell survival and radioresistance of prostate cancer cells when exposed to ionizing radiation. The results shed a new light into the development of future translational treatment strategies for prostate cancer patients during radiation therapy.
Key words: IGF-IR, prostate cancer, radioresistance, survival