ANTISENSE RNA TO THE TYPE I INSULIN-LIKE GROWTH FACTOR RECEPTOR REVERSED THE TRANSFORMED PHENOTYPE OF PC-3 HUMAN PROSTATE CANCER CELL LINE IN VITRO

The insulin-like growth factor I receptor (IGF-IR) plays an essential role in the establishment and maintenance of transformed phenotype. Interference with the IGF-IR pathway by antisense causes reversal of the transformed phenotype in many rodent and human tumor cell lines. We stably transfected the PC-3 human prostate cancer cell line with an IGF-IR antisense RNA expression plasmid. The number of IGF-I receptors on the antisense-transfected PC-3 cells was reduced by 40.2% relative to the control-transfected cells. The transfected cells maintained their high expression of IGF-IR antisense RNA for up to one year in selective medium . The reduction in the expression of IGF-IR had no effect on the cell growth in monolayer. The clonogenicity of antisense-transfected cells was 24.7% of the clonogenicity of control-transfected cells in soft agar. There was a good correlation between IGF-IR level and inhibition of transformation in soft agar. These results indicate that reduction of IGF-IR by antisense RNA can reverse the transformed phenotype of human prostate cancer cells.