Novel RNA- or Antibody-Based Strategies Targeting Growth Factors in Prostate Cancer

摘要

PC-3 cells expressing active IGF-II ribozymes do not grow or are prone to die under the serum-free or low serum whereas PC-3 cells expressing the inactive ribozyme or vector only grew and survived. Inhibition of IGF-II/IGFIR signaling by intracellular expression of IGF-II ribozyme only reduced endogenous IGF-II levels to 40% of control levels. Their results not only confirmed our hypothesis that IGF-II plays a critical role in prostate cancer growth, but also suggested that complete inhibition of the IGF-II/IGFIR signaling cannot be achieved since this signaling is absolutely required for PC-3 cell growth. This is most likely the reason why we were not able to isolate stable clones. Thus, as alternative, we tried inducible expression system and retrovirus-mediated transfer of ribozymes or alpha IGFIR scFvs. Inducible or transient expression, which we planned to do, did not result in good outcomes. Stable clones expressing active and inactive ribozymes from prostate cancer PC-3, LNCaP, DU145, and M12 infected by retrovirus were then isolated and characterized (manuscript in preparation). Prostate cancer cells expressing alpha IGFIR scFvs have been studied by a new collaborator, Dr. Sikes.